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Tamas Bartfai - One of the best experts on this subject based on the ideXlab platform.
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Galanin Receptors and Ligands
Frontiers in Endocrinology, 2012Co-Authors: Kristin Webling, Tamas Bartfai, Johan Runesson, Ulo LangelAbstract:The neuropeptide Galanin was first discovered 30 years ago. Today, the Galanin family consists of Galanin, Galanin-like peptide (GALP), Galanin-message associated peptide (GMAP), and alarin and this family has been shown to be involved in a wide variety of biological and pathological functions. The effect is mediated through three GPCR subtypes, GalR1-3. The limited number of specific ligands to the Galanin receptor subtypes has hindered the understanding of the individual effects of each receptor subtype. This review aims to summarize the current data of the importance of the Galanin receptor subtypes and receptor subtype specific agonists and antagonists and their involvement in different biological and pathological functions.
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receptor subtype dependent Galanin actions on gamma aminobutyric acidergic neurotransmission and ethanol responses in the central amygdala
Addiction Biology, 2012Co-Authors: Michal Bajo, Tamas Bartfai, Samuel G Madamba, Lisa M Sharkey, G R SigginsAbstract:The neuropeptide Galanin and its three receptor subtypes (GalR1-3) are expressed in the central amygdala (CeA), a brain region involved in stress- and anxiety-related behaviors, as well as alcohol dependence. Galanin also has been suggested to play a role in alcohol intake and alcohol dependence. We examined the effects of Galanin in CeA slices from wild-type and knockout (KO) mice deficient of GalR2 and both GalR1 and GalR2 receptors. Galanin had dual effects on gamma-aminobutyric acid (GABA)-ergic transmission, decreasing the amplitudes of pharmacologically isolated GABAergic inhibitory postsynaptic potentials (IPSPs) in over half of CeA neurons but augmenting IPSPs in the others. The increase in IPSP size was absent after superfusion of the GalR3 antagonist SNAP 37889, whereas the IPSP depression was absent in CeA neurons of GalR1 × GalR2 double KO and GalR2 KO mice. Paired-pulse facilitation studies showed weak or infrequent effects of Galanin on GABA release. Thus, Galanin may act postsynaptically through GalR3 to augment GABAergic transmission in some CeA neurons, whereas GalR2 receptors likely are involved in the depression of IPSPs. Co-superfusion of ethanol, which augments IPSPs presynaptically, together with Galanin caused summated effects of ethanol and Galanin in those CeA neurons showing Galanin-augmented IPSPs, suggesting the two agents act via different mechanisms in this population. However, in neurons showing IPSP-diminishing Galanin effects, Galanin blunted the ethanol effects, suggesting a preemptive effect of Galanin. These findings may increase understanding of the complex cellular mechanisms that underlie the anxiety-related behavioral effects of Galanin and ethanol in CeA.
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Korea
2012Co-Authors: Ulo Langel, Tamas Bartfai, Johan Runesson, Sebastien G Bouret, Jong-ik Hwang, Kristin WeblingAbstract:su.se The neuropeptide Galanin was first discovered 30 years ago. Today, the Galanin family con-sists of Galanin, Galanin-like peptide (GALP), Galanin-message associated peptide (GMAP), and alarin and this family has been shown to be involved in a wide variety of biological and pathological functions.The effect is mediated through three GPCR subtypes, GalR1-3. The limited number of specific ligands to the Galanin receptor subtypes has hindered the understanding of the individual effects of each receptor subtype.This review aims to sum-marize the current data of the importance of the Galanin receptor subtypes and receptor subtype specific agonists and antagonists and their involvement in different biological and pathological functions
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bidirectional regulation of stress responses by Galanin in mice involvement of Galanin receptor subtype 1
Neuroscience, 2009Co-Authors: Kayo Mitsukawa, Tamas BartfaiAbstract:The neuropeptide Galanin has been shown to play a role in psychiatric disorders as well as in other biological processes including regulation of pain threshold through interactions with three G-protein coupled receptors, Galanin receptor subtypes 1-3 (GalR1-3). While most of the pharmacological studies on Galanin in stress-related disorders have been done with rats, the continuous development of genetically engineered mice involving Galanin or its receptor subtype(s) validates the importance of mouse pharmacological studies. The present study on mice examined the homeostatic, endocrinological and neuroanatomical effects of the Galanin, injected intracerebroventricularly (i.c.v.), in regulation of stress responses after restraint stress. Furthermore, the roles of GalR1 on these effects were studied using GalR1 knockout (KO) mice. The core body temperature and the locomotor activity were monitored with radio telemetry devices. Galanin (i.c.v.) decreased locomotor activity and exerted a bidirectional effect on the restraint stress-induced hyperthermia; a high dose of Galanin significantly attenuated the stress-induced hyperthermic response, while a low dose of Galanin moderately enhanced this response. The bidirectional effect of Galanin was correlated with changes in stress hormone levels (adrenocorticotropic hormone and corticosterone). To neuroanatomically localize the effects of Galanin on stress response, cFos immunoreactivity was assessed in Galanin receptor rich areas; paraventricular nucleus (PVN) of the hypothalamus and the locus coeruleus (LC), respectively. A high dose of Galanin significantly induced cFos activity in the LC but not in the PVN. In GalR1KO mice, a high dose of Galanin failed to induce any of the above effects, suggesting the pivotal role of GalR1 in decreased locomotor activity and stress-resistant effects caused by Galanin i.c.v. injection studied here.
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Galanin 2 11 binds to galr3 in transfected cell lines limitations for pharmacological definition of receptor subtypes
Neuropeptides, 2005Co-Authors: Linda Lundström, Tamas BartfaiAbstract:Abstract The neuropeptide Galanin regulates a variety of physiological and pathophysiological processes through three G protein coupled receptors, GalR1, GalR2, and GalR3. The studies on Galanin receptor subtype specific effects have been hampered by the lack of high affinity subtype selective antagonist and/or agonist to any of these three Galanin receptor subtypes. Since its recent introduction in 2003, Galanin (2–11) has been widely used as a GalR2 selective agonist in several in vitro and in vivo studies. In the present paper, we demonstrate that Galanin (2–11) binds to rat GalR3 receptors in transfected cell lines with a similar affinity as it binds to GalR2. As none of the available antagonists are Galanin receptor subtype selective, as shown here for M35 and M40, more work is needed to confirm whether a Galanin (2–11) effect is GalR2 mediated and there is an urgent need for high affinity Galanin receptor subtype selective ligands. For now one needs to interpret the data obtained at lower Galanin (2–11) concentrations as effects mediated by non-GalR1 type Galanin receptors, i.e., GalR2 and/or GalR3.
Kjell Fuxe - One of the best experts on this subject based on the ideXlab platform.
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the neuropeptides Galanin and Galanin 1 15 in depression like behaviours
Neuropeptides, 2017Co-Authors: Carmelo Millón, Manuel Narváez, Kjell Fuxe, José Ángel Narváez, Antonio Floresburgess, Dasiel O Borrotoescuela, Belen Gago, Luis J Santin, Estela Castillaortega, Zaida DiazcabialeAbstract:Galanin is a 29 amino acid neuropeptide widely distributed in neurons within the central nervous system. Galanin exerts its biological activities through three different G protein-receptors and participates in a number of functions, including mood regulation. Not only Galanin but also Galanin N-terminal fragments like Galanin(1-15) are active at the central level. In this work, we review the latest findings in studies on Galanin and Galanin(1-15) in depression-related behaviours. Our focus is on animal models for depression, and we pay some attention to research data obtained in human studies. Since Serotonin (5-HT), especially through 5-HT1A, and Galanin receptors interact at both pre-and postsynaptic level, the development of drugs targeting potential GAL1-GAL2-5-HT1A heteroreceptor complexes linked to the raphe-hippocampal 5-HT neurons may represent new treatment strategies in depression.
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Galanin receptor neuropeptide y receptor interactions in the central nervous system
Current Protein & Peptide Science, 2014Co-Authors: Zaida Diazcabiale, Manuel Narváez, Carmelo Millón, Concepción Parrado, Araceli Puigcerver, Rafael Coveñas, Kjell Fuxe, Antonio Floresburgess, José Ángel NarváezAbstract:The presence of Galanin and Neuropeptide Y and/or their receptors in several areas of the brain involved in memory, mood, cardiovascular control and food intake indicates that Galanin, and Neuropeptide Y could equilibrate the physiological actions of each other. There is evidence for the existence of interactions between Galanin Receptor and Neuropeptide Y Receptor in the nucleus of the solitarii tract (NTS), hypothalamus and dorsal raphe nucleus probably taking place with the formation of heteromers between Galanin Receptor and Neuropeptide Y Y1 Receptor. The Galanin fragment (Gal 1-15) preferring receptors may instead be formed by the GalR1-GalR2 heteromer which in the NTS may interact with Neuropeptide Y Y2 receptors. These receptor heteromers may be one key molecular mechanism for Galanin and its N-terminal fragment (Galanin 1-15) to modulate the function of different types of glia-neuronal networks in the CNS, especially the emotional, metabolic and cardiovascular networks.
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the Galanin receptor antagonist m40 blocks the central cardiovascular actions of the Galanin n terminal fragment 1 15
European Journal of Pharmacology, 2000Co-Authors: José Ángel Narváez, Rafael Coveñas, Zaida Diazcabiale, Peter B Hedlund, J A Aguirre, S Gonzalezbaron, Kjell FuxeAbstract:It has been shown that Galanin plays a role in central cardiovascular regulation. Galanin administered centrally induces an increase of heart rate and a weak vasodepressor response, whereas the N-terminal Galanin fragment (1–15) elicits vasopressor effects and tachycardia. Furthermore, it has been shown that Galanin-(1–15), but not Galanin-(1–29), decreases the baroreceptor reflex sensitivity. Since these data demonstrate that both Galanin and its N-terminal fragment (1–15) exert a different modulation on central cardiovascular control, the aim of this work has been to study if the specific Galanin receptor antagonist Galanin-(1–12)-Pro-(Ala-Leu)2-Ala]-amide (M40) could modulate their cardiovascular actions. Urethane anaesthetized rats were injected intracisternally and the changes in mean arterial pressure and heart rate were monitored. Two doses of M40 alone have been tested for their cardiovascular effects. With the dose of 1.0 nmol, a significant tachycardia was observed (P<0.001), but 0.1 nmol was ineffective. This suggests a possible agonistic effect for the higher doses of M40. The Galanin receptor antagonist M40 at the dose of 0.1 nmol failed to modify the weak vasodepressor effects and tachycardia induced by 3.0 nmol of Galanin-(1–29). However, the same dose completely blocked the vasopressor and tachycardic responses elicited by 3.0 nmol of Galanin-(1–15). These data show that M40 differentially counteracts the central cardiovascular responses of the Galanin fragment and give a functional support for the existence of Galanin receptor subtypes within the brainstem. Therefore, the present findings can be explained on the basis that the cardiovascular actions of Galanin-(1–29) could be mediated by one type of Galanin receptor, whereas a Galanin receptor subtype that recognizes N-terminal fragments of Galanin may mediate the actions of Galanin-(1–15).
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Galanin 1 16 modulates 5 htia receptors in the ventral limbic cortex of the rat
Neuroreport, 2000Co-Authors: Zaida Diazcabiale, José Ángel Narváez, S O Ogren, Ullabritt Finnman, Inmaculada Bellido, Kjell FuxeAbstract:The aim of the present study was to evaluate whether Galanin-(1-16) of the rat and porcine type and rat Galanin-(1-29) can modulate the 5-HT1A receptors, using [3H]8-OH-DPAT as a radioligand, in membrane preparations from the ventral limbic cortex of the rat. Galanin-(1-16) produced a concentration dependent increase in the Kd value of [3H]8-OH-DPAT binding sites with a maximal effect of approximately 61% at 30 nM without changing the Bmax values. The Galanin antagonist M35 blocked these effects. Rat Galanin produced the same pattern of response but was less potent and effective. These results indicate the existence of a Galanin receptor subtype in the ventral limbic cortex mainly recognizing N-terminal Galanin fragments and capable of more strongly modulating 5-HT1A receptors than cloned Galanin receptors.
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centrally infused Galanin 1 15 but not Galanin 1 29 reduces the baroreceptor reflex sensitivity in the rat
Brain Research, 1996Co-Authors: Zaida Diaz, J A Narvaez, Peter B Hedlund, J A Aguirre, S Gonzalezbaron, Kjell FuxeAbstract:Abstract It has been demonstrated previously that central administration of the N-terminal Galanin fragment (1–15) elicits hypertension and tachycardia and antagonizes the hypotensive effect of the parent molecule Galanin-(1–29). In order to further clarify the role of Galanin in central cardiovascular control, the possible modulation of the baroreceptor reflex by both Galanin molecules has been studied. Different groups of rats were injected in the lateral ventricle with subthreshold doses of Galanin-(1–15) (0.1 nmol/rat, or 0.3 nmol/rat), with subthreshold doses of Galanin-(1–29) (0.1 nmol/rat, and 0.3 nmol/rat) or with an effective dose of Galanin-(1–29) (3.0 nmol/rat). The baroreceptor reflex was elicited by intravenous injections of different doses of l -phenylephrine before and after the intraventricular administration of Galanin peptides. The changes of the bradycardic responses after Galanin peptide injections as well as the modifications of the baroreceptor reflex sensitivity were evaluated. Intraventricular injections of Galanin-(1–15) significantly inhibited the reflex bradycardia elicited by intravenous l -phenylephrine and thus decreased the baroreceptor sensitivity. However, neither subthreshold doses of Galanin-(1–29) nor its effective dose were able to modulate these cardiovascular responses. From these data it may be suggested that the Galanin fragment (1–15) plays a more important role in central cardiovascular regulation than Galanin-(1–29), possibly acting on a specific receptor subtype which exclusively recognizes N-terminal fragments of Galanin, and exists on cardiovascular areas of the central nervous system.
Takashi Yoshitake - One of the best experts on this subject based on the ideXlab platform.
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correlation between the effects of local and intracerebroventricular infusions of Galanin on 5 ht release studied by microdialysis and distribution of Galanin and Galanin receptors in prefrontal cortex ventral hippocampus amygdala hypothalamus and striatum of awake rats
Synapse, 2014Co-Authors: Shimako Yoshitake, Eugenia Kuteeva, Tomas Hokfelt, Francoise Mennicken, Elvar Theodorsson, Masatoshi Yamaguchi, Jan Kehr, Takashi YoshitakeAbstract:The neuropeptide Galanin is implicated in regulation of affective behavior, including modulation of 5-HT signaling. Here, we investigated, by use of microdialysis in freely moving rats, the effects of intracerebral (i.c.) and intracerebroventricular (i.c.v.) infusions of Galanin on basal extracellular 5-HT levels in medial prefrontal cortex (mPFC), CA1 area of ventral hippocampus (vHPC), central amygdaloid nucleus (CeA), ventromedial hypothalamic nucleus ventrolateral part (VMHvl), and ventromedial caudate putamen (CPu). These results were compared with a parallel immunohistochemical analysis of the distribution of Galanin, 5-HT, and noradrenaline (NA) nerve terminals, and with data on Galanin receptors. Galanin i.c.v. significantly decreased the 5-HT levels in mPFC to 79% and in vHPC to 72%. Local infusions of Galanin caused a long-lasting decrease in 5-HT levels in vHPC to 88%, and a moderate decrease in CeA, whereas the 5-HT levels in mPFC significantly increased to 121%. These effects of i.c. Galanin correlated well with the density of 5-HT and Galanin nerve terminals and Galanin receptors autoradiography in mPFC, vHPC, and CeA. No effects of i.c. or i.c.v. Galanin on 5-HT levels were observed in CPu or VMHvl, in agreement with the low numbers of Galanin-positive terminals and low/moderate Galanin receptor density. Galanin was often found to coexist in NA, but could never be detected in 5-HT terminals. Together the results show a neuroanatomical correlation between the effects of Galanin infusions on 5-HT release and distribution of Galanin and its receptors, and that i.c.v. and i.c. administration can give opposite effects on 5-HT release.
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correlation between the effects of local and intracerebroventricular infusions of Galanin on 5 ht release studied by microdialysis and distribution of Galanin and Galanin receptors in prefrontal cortex ventral hippocampus amygdala hypothalamus and striatum of awake rats
Synapse, 2014Co-Authors: Shimako Yoshitake, Eugenia Kuteeva, Tomas Hokfelt, Francoise Mennicken, Elvar Theodorsson, Masatoshi Yamaguchi, Jan Kehr, Takashi YoshitakeAbstract:The neuropeptide Galanin is implicated in regulation of affective behavior, including modulation of 5-HT signaling. Here, we investigated, by use of microdialysis in freely moving rats, the effects of intracerebral (i.c.) and intracerebroventricular (i.c.v.) infusions of Galanin on basal extracellular 5-HT levels in medial prefrontal cortex (mPFC), CA1 area of ventral hippocampus (vHPC), central amygdaloid nucleus (CeA), ventromedial hypothalamic nucleus ventrolateral part (VMHvl), and ventromedial caudate putamen (CPu). These results were compared with a parallel immunohistochemical analysis of the distribution of Galanin, 5-HT, and noradrenaline (NA) nerve terminals, and with data on Galanin receptors. Galanin i.c.v. significantly decreased the 5-HT levels in mPFC to 79% and in vHPC to 72%. Local infusions of Galanin caused a long-lasting decrease in 5-HT levels in vHPC to 88%, and a moderate decrease in CeA, whereas the 5-HT levels in mPFC significantly increased to 121%. These effects of i.c. Galanin correlated well with the density of 5-HT and Galanin nerve terminals and Galanin receptors autoradiography in mPFC, vHPC, and CeA. No effects of i.c. or i.c.v. Galanin on 5-HT levels were observed in CPu or VMHvl, in agreement with the low numbers of Galanin-positive terminals and low/moderate Galanin receptor density. Galanin was often found to coexist in NA, but could never be detected in 5-HT terminals. Together the results show a neuroanatomical correlation between the effects of Galanin infusions on 5-HT release and distribution of Galanin and its receptors, and that i.c.v. and i.c. administration can give opposite effects on 5-HT release. Synapse 68:179–193, 2014. © 2014 Wiley Periodicals, Inc.
Ulo Langel - One of the best experts on this subject based on the ideXlab platform.
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Galanin Receptors and Ligands
Frontiers in Endocrinology, 2012Co-Authors: Kristin Webling, Tamas Bartfai, Johan Runesson, Ulo LangelAbstract:The neuropeptide Galanin was first discovered 30 years ago. Today, the Galanin family consists of Galanin, Galanin-like peptide (GALP), Galanin-message associated peptide (GMAP), and alarin and this family has been shown to be involved in a wide variety of biological and pathological functions. The effect is mediated through three GPCR subtypes, GalR1-3. The limited number of specific ligands to the Galanin receptor subtypes has hindered the understanding of the individual effects of each receptor subtype. This review aims to summarize the current data of the importance of the Galanin receptor subtypes and receptor subtype specific agonists and antagonists and their involvement in different biological and pathological functions.
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Korea
2012Co-Authors: Ulo Langel, Tamas Bartfai, Johan Runesson, Sebastien G Bouret, Jong-ik Hwang, Kristin WeblingAbstract:su.se The neuropeptide Galanin was first discovered 30 years ago. Today, the Galanin family con-sists of Galanin, Galanin-like peptide (GALP), Galanin-message associated peptide (GMAP), and alarin and this family has been shown to be involved in a wide variety of biological and pathological functions.The effect is mediated through three GPCR subtypes, GalR1-3. The limited number of specific ligands to the Galanin receptor subtypes has hindered the understanding of the individual effects of each receptor subtype.This review aims to sum-marize the current data of the importance of the Galanin receptor subtypes and receptor subtype specific agonists and antagonists and their involvement in different biological and pathological functions
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Galanin receptor agonists protect against kainic acid-induced excitotoxicity in the rat hippocampus
2011Co-Authors: Jessica L. Groves-chapman, Ulo Langel, Johan Runesson, Philip V. HolmesAbstract:Galanin is a peptide neurotransmitter with neuroprotective actions. Administration of Galanin or selective Galanin receptor agonists to rats reduces convulsant-induced seizure behavior. However, it ...
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intracerebroventricular administration of Galanin or Galanin receptor subtype 1 agonist m617 induces c fos activation in central amygdala and dorsomedial hypothalamus
Peptides, 2007Co-Authors: Alice L Blackshear, Ulo Langel, Linda Lundström, Philip V. Holmes, Mihoko Yamamoto, Brenda J Anderson, John K RobinsonAbstract:The neuropeptide Galanin and Galanin receptors are widespread throughout cortical, limbic and midbrain areas implicated in reward, learning/memory, pain, drinking and feeding. While many studies have shown that Galanin produces a variety of presynaptic and post-synaptic responses, work studying the effects of Galanin on neural activation is limited. The present study examined patterns of c-Fos immunoreactivity resulting from intracerebroventricular administration of Galanin versus saline injection in awake rats. An initial comprehensive qualitative survey was conducted to identify regions of high c-Fos expression followed up with quantitative analysis. Galanin induced a significant increase in c-Fos levels relative to saline-treated controls in dorsomedial hypothalamus and in the central nucleus of the amygdala. This pattern of activation was also produced by Galanin receptor type 1 agonist M617. The present findings confirm that Galanin upregulates c-Fos activation in hypothalamic nuclei, and supports roles for Galanin in central amygdala-mediated regulation of stress-responses, food intake, and Pavlovian conditioning.
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regulation of kindling epileptogenesis by hippocampal Galanin type 1 and type 2 receptors the effects of subtype selective agonists and the role of g protein mediated signaling
Journal of Pharmacology and Experimental Therapeutics, 2006Co-Authors: Andrey Mazarati, Ulo Langel, Linda Lundström, Don Shin, Ulla E Sollenberg, Raman SankarAbstract:The search for antiepileptic drugs that are capable of blocking the progression of epilepsy (epileptogenesis) is an important problem of translational epilepsy research. The neuropeptide Galanin effectively suppresses acute seizures. We examined the ability of hippocampal Galanin receptor type 1 (GalR1) and type 2 (GalR2) to inhibit kindling epileptogenesis and studied signaling cascades that mediate their effects. Wistar rats received 24-h-long intrahippocampal infusion of a GalR1/2 agonist Galanin(1-29), GalR1 agonist M617 [Galanin(1-13)-Gln14-bradykinin(2-9)-amide], or GalR2 agonist Galanin(2-11). The peptides were administered alone or combined with an inhibitor of Gi protein pertussis toxin (PTX), Gi-protein activated K+ channels (GIRK) inhibitor tertiapin Q (TPQ), Gq/11 protein inhibitor [d-Arg1,d-Trp5,7,9,Leu11]-substance P (dSP), or an inhibitor of intracellular Ca2+ release dantrolene. Sixteen hours into drug delivery, the animals were subjected to rapid kindling—60 electrical trains administered to ventral hippocampus every 5 min. M617 delayed epileptogenesis, whereas Galanin(1-29) and Galanin(2-11) completely prevented the occurrence of full kindled seizures. TPQ abolished anticonvulsant effect of M617 but not of Galanin(2-11). PTX blocked anticonvulsant effects of M617 and inversed the action of Galanin(1-29) and Galanin(2-11) to proconvulsant. dSP and dantrolene did not modify seizure suppression through GalR1 and GalR2, but eliminated the proconvulsant effect of PTX + Galanin(1-29) and PTX + Galanin(2-11) combinations. We conclude that hippocampal GalR1 exert their disease-modifying effect through the Gi-GIRK pathway. GalR2 is antiepileptogenic through the Gi mechanism independent of GIRK. A secondary proconvulsant pathway coupled to GalR2 involves Gq/11 and intracellular Ca2+. The data are important for understanding endogenous mechanisms regulating epileptogenesis and for the development of novel antiepileptogenic drugs.
Tomas Hokfelt - One of the best experts on this subject based on the ideXlab platform.
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injection of Galanin into the dorsal hippocampus impairs emotional memory independent of 5 ht1a receptor activation
Behavioural Brain Research, 2021Co-Authors: Eugenia Kuteeva, Oliver Stiedl, Tomas Hokfelt, Sven Ove OgrenAbstract:Abstract There is evidence that interaction between the neuropeptide Galanin and the 5-HT1A receptor represents an integrative mechanism in the regulation of serotonergic neurotransmission. Thus, in rats intracerebroventricular (i.c.v.) Galanin did not impair retention in the passive avoidance (PA) test 24 h after training, but attenuated the retention deficit caused by subcutaneous (s.c.) administration of the 5-HT1A receptor agonist 8-OH-DPAT. This impairment has been linked to postsynaptic 5-HT1A receptor activation. To confirm these results in mice, Galanin was infused i.c.v. (1 nmol/mouse) in C57BL/6/Bkl mice 30 min prior to training followed by s.c. injection (0.3 mg/kg) of 8-OH-DPAT or saline 15 min before PA training. In line with previous results, i.c.v. Galanin significantly attenuated the PA impairment caused by 5-HT1A receptor activation in mice. To study if the Galanin 5-HT1A receptor interaction involved the dorsal hippocampus, Galanin (1 nmol/mouse) was directly infused into this brain region alone or in combination with s.c. 8-OH-DPAT. However, unlike i.c.v. Galanin, Galanin infusion into the dorsal hippocampus alone impaired PA retention and failed to attenuate the 8-OH-DPAT-mediated PA impairment. These results indicate that the ability of i.c.v. Galanin to modify 5-HT1A receptor activation is not directly mediated via receptor interactions in the dorsal hippocampus. Instead, the Galanin-mediated PA impairment suggests an important inhibitory role of Galanin receptors in the dorsal hippocampus for acquisition (encoding) and/or consolidation of emotional memory. In addition, the interaction between Galanin and 5-HT1A receptors probably involves a wide serotonergic network that is important for the integration of emotional and cognitive behaviors.
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physiology signaling and pharmacology of Galanin peptides and receptors three decades of emerging diversity
Pharmacological Reviews, 2015Co-Authors: Roland Lang, David Wynick, Fiona E Holmes, Tomas Hokfelt, Andrew L Gundlach, Sally A Hobson, Barbara KoflerAbstract:Galanin was first identified 30 years ago as a "classic neuropeptide," with actions primarily as a modulator of neurotransmission in the brain and peripheral nervous system. Other structurally-related peptides-Galanin-like peptide and alarin-with diverse biologic actions in brain and other tissues have since been identified, although, unlike Galanin, their cognate receptors are currently unknown. Over the last two decades, in addition to many neuronal actions, a number of nonneuronal actions of Galanin and other Galanin family peptides have been described. These include actions associated with neural stem cells, nonneuronal cells in the brain such as glia, endocrine functions, effects on metabolism, energy homeostasis, and paracrine effects in bone. Substantial new data also indicate an emerging role for Galanin in innate immunity, inflammation, and cancer. Galanin has been shown to regulate its numerous physiologic and pathophysiological processes through interactions with three G protein-coupled receptors, GAL1, GAL2, and GAL3, and signaling via multiple transduction pathways, including inhibition of cAMP/PKA (GAL1, GAL3) and stimulation of phospholipase C (GAL2). In this review, we emphasize the importance of novel Galanin receptor-specific agonists and antagonists. Also, other approaches, including new transgenic mouse lines (such as a recently characterized GAL3 knockout mouse) represent, in combination with viral-based techniques, critical tools required to better evaluate Galanin system physiology. These in turn will help identify potential targets of the Galanin/Galanin-receptor systems in a diverse range of human diseases, including pain, mood disorders, epilepsy, neurodegenerative conditions, diabetes, and cancer.
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correlation between the effects of local and intracerebroventricular infusions of Galanin on 5 ht release studied by microdialysis and distribution of Galanin and Galanin receptors in prefrontal cortex ventral hippocampus amygdala hypothalamus and striatum of awake rats
Synapse, 2014Co-Authors: Shimako Yoshitake, Eugenia Kuteeva, Tomas Hokfelt, Francoise Mennicken, Elvar Theodorsson, Masatoshi Yamaguchi, Jan Kehr, Takashi YoshitakeAbstract:The neuropeptide Galanin is implicated in regulation of affective behavior, including modulation of 5-HT signaling. Here, we investigated, by use of microdialysis in freely moving rats, the effects of intracerebral (i.c.) and intracerebroventricular (i.c.v.) infusions of Galanin on basal extracellular 5-HT levels in medial prefrontal cortex (mPFC), CA1 area of ventral hippocampus (vHPC), central amygdaloid nucleus (CeA), ventromedial hypothalamic nucleus ventrolateral part (VMHvl), and ventromedial caudate putamen (CPu). These results were compared with a parallel immunohistochemical analysis of the distribution of Galanin, 5-HT, and noradrenaline (NA) nerve terminals, and with data on Galanin receptors. Galanin i.c.v. significantly decreased the 5-HT levels in mPFC to 79% and in vHPC to 72%. Local infusions of Galanin caused a long-lasting decrease in 5-HT levels in vHPC to 88%, and a moderate decrease in CeA, whereas the 5-HT levels in mPFC significantly increased to 121%. These effects of i.c. Galanin correlated well with the density of 5-HT and Galanin nerve terminals and Galanin receptors autoradiography in mPFC, vHPC, and CeA. No effects of i.c. or i.c.v. Galanin on 5-HT levels were observed in CPu or VMHvl, in agreement with the low numbers of Galanin-positive terminals and low/moderate Galanin receptor density. Galanin was often found to coexist in NA, but could never be detected in 5-HT terminals. Together the results show a neuroanatomical correlation between the effects of Galanin infusions on 5-HT release and distribution of Galanin and its receptors, and that i.c.v. and i.c. administration can give opposite effects on 5-HT release.
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correlation between the effects of local and intracerebroventricular infusions of Galanin on 5 ht release studied by microdialysis and distribution of Galanin and Galanin receptors in prefrontal cortex ventral hippocampus amygdala hypothalamus and striatum of awake rats
Synapse, 2014Co-Authors: Shimako Yoshitake, Eugenia Kuteeva, Tomas Hokfelt, Francoise Mennicken, Elvar Theodorsson, Masatoshi Yamaguchi, Jan Kehr, Takashi YoshitakeAbstract:The neuropeptide Galanin is implicated in regulation of affective behavior, including modulation of 5-HT signaling. Here, we investigated, by use of microdialysis in freely moving rats, the effects of intracerebral (i.c.) and intracerebroventricular (i.c.v.) infusions of Galanin on basal extracellular 5-HT levels in medial prefrontal cortex (mPFC), CA1 area of ventral hippocampus (vHPC), central amygdaloid nucleus (CeA), ventromedial hypothalamic nucleus ventrolateral part (VMHvl), and ventromedial caudate putamen (CPu). These results were compared with a parallel immunohistochemical analysis of the distribution of Galanin, 5-HT, and noradrenaline (NA) nerve terminals, and with data on Galanin receptors. Galanin i.c.v. significantly decreased the 5-HT levels in mPFC to 79% and in vHPC to 72%. Local infusions of Galanin caused a long-lasting decrease in 5-HT levels in vHPC to 88%, and a moderate decrease in CeA, whereas the 5-HT levels in mPFC significantly increased to 121%. These effects of i.c. Galanin correlated well with the density of 5-HT and Galanin nerve terminals and Galanin receptors autoradiography in mPFC, vHPC, and CeA. No effects of i.c. or i.c.v. Galanin on 5-HT levels were observed in CPu or VMHvl, in agreement with the low numbers of Galanin-positive terminals and low/moderate Galanin receptor density. Galanin was often found to coexist in NA, but could never be detected in 5-HT terminals. Together the results show a neuroanatomical correlation between the effects of Galanin infusions on 5-HT release and distribution of Galanin and its receptors, and that i.c.v. and i.c. administration can give opposite effects on 5-HT release. Synapse 68:179–193, 2014. © 2014 Wiley Periodicals, Inc.
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the participation of Galanin in pain processing at the spinal level
Trends in Pharmacological Sciences, 2002Co-Authors: Hongxiang Liu, Tomas HokfeltAbstract:Galanin, a 29-amino-acid peptide expressed in dorsal root ganglia (DRG) and spinal dorsal horn interneurones, is regulated by nerve injury and peripheral inflammation. The functional significance of such regulation has been subject to intense studies, including the analysis of Galanin null mice, with the production of apparently conflicting results. Here, we suggest that upregulation of Galanin in DRG neurones following nerve injury results in antinociception via stimulation of Galanin GAL1 receptors on dorsal horn neurones, and that the pro-nociceptive effect of Galanin is related to presynaptic Galanin GAL2 receptors on primary afferents. A selective GAL1 receptor agonist could therefore be valuable for the treatment of neuropathic pain.
