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Francis W. Flynn - One of the best experts on this subject based on the ideXlab platform.
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Activation of the neurokinin 3 receptor promotes filopodia growth and sprouting in rat embryonic hypothalamic cells.
Developmental Neurobiology, 2014Co-Authors: Francis W. Flynn, Eli Kinney-lang, Chelsea Hoekstra, Donald L. Pratt, Amit ThakarAbstract:Members of the tachykinin family have trophic effects on developing neurons. The tachykinin neurokinin 3 receptor (NK3R) appears early in embryonic development; during the peak birthdates of hypothalamic neurons, but its involvement in neural development has not been examined. To address its possible role, immortalized embryonic hypothalamic neurons (CLU209) were treated with CellMask, a plasma membrane stain, or the membranes were imaged in CLU209 cells that were transfected with a pEGFP-NK3R expression vector. Nontransfected cells and transfected cells were then treated with Senktide, a NK3R agonist, or Dulbecco's Modified Eagle's Medium (DMEM) and time-lapse confocal images were captured for the following 30 min. Compared to DMEM, Senktide treatment led to filopodia initiation from the soma of both nontransfected and transfected CLU209 cells. These filopodia had diameters and lengths of approximately 200 nm and 3 µm, respectively. Pretreatment with an IP3 receptor blocker, 2-aminoethoxydiphenyl borate (2-APB), prevented the Senktide-induced growth in filopodia; demonstrating that NK3R-induced outgrowth of filopodia likely involves the release of intracellular calcium. Exposure of transfected CLU209 cells to Senktide for 24 h led to further growth of filopodia and processes that extended 10-20 µm. A mathematical model, composed of a linear and population model was developed to account for the dynamics of filopodia growth during a timescale of minutes. The results suggest that the ligand-induced activation of NK3R affects early developmental processes by initiating filopodia formation that are a prerequisite for neuritogenesis.
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Activation of tachykinin, neurokinin 3 receptors affects chromatin structure and gene expression by means of histone acetylation
Peptides, 2012Co-Authors: Amit Thakar, Elise Sylar, Francis W. FlynnAbstract:The tachykinin, neurokinin 3 receptor (NK3R) is a g-protein coupled receptor that is broadly distributed in the nervous system and exerts its diverse physiological actions through multiple signaling pathways. Despite the role of the receptor system in a range of biological functions, the effects of NK3R activation on chromatin dynamics and gene expression have received limited attention. The present work determined the effects of Senktide, a selective NK3R agonist, on chromatin organization, acetylation, and gene expression, using qRT-PCR, in a hypothalamic cell line (CLU 209) that expresses the NK3R. Senktide (1 nM, 10nM) caused a relaxation of chromatin, an increase in global acetylation of histone H3 and H4, and an increase in the expression of a common set of genes involved in cell signaling, cell growth, and synaptic plasticity. Pretreatment with histone acetyltransferase (HAT) inhibitor (garcinol and 2-methylene y-butylactone), that inhibits p300, p300/CREB binding protein (CBP) associated factor (PCAF), and GCN 5, prevented the Senktide-induced increase in expression of most, but not all, of the genes upregulated in response to 1 nM and 10nM Senktide. Treatment with 100 nM had the opposite effect: a reduction in chromatin relaxation and decreased acetylation. The expression of four genes was significantly decreased and the HAT inhibitor had a limited effect in blocking the upregulation of genes in response to 100 nM Senktide. Activation of the NK3R appears to recruit multiple pathways, including acetylation, and possibly histone deactylases, histone methylases, or DNA methylases to affect chromatin structure and gene expression.
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Central injections of tachykinin NK3 receptor agonists inhibit salt appetite and cause translocation of the NK3 receptor to the nuclei of neurons in the paraventricular nucleus of the hypothalamus.
Appetite, 2007Co-Authors: Francis W. Flynn, G.e. Haley, D.d. Jensen, K. Schamber, D. PrattAbstract:Central, intraventricular injections of tachykinin NK3 receptor (NK3R) agonists inhibit the ingestion of sodium containing solutions under need-free and need-induced conditions. NK3R are internalized within the cell following agonist binding and as such, the translocation of the receptor provides a means by which to identify NK3R expressing neurons that are activated by the intraventricular injection. Male, Charles River Laboratory rats were fitted with lateral ventricle cannulas and maintained on chow and water. Rats were administered intraventricular injections of isotonic saline or 200 ng Senktide, a selective NK3R agonist, and then given access to 0.15 M NaCl. A separate group of rats were also treated with saline or Senktide, and sacrificed 5, 20 or 120 min later, and the brains processed for NK3R immunoreactivity (IR). Intraventricular injections of Senktide significantly suppressed the ingestion of NaCl during the first 20 min of the test. Confocal examination of the paraventricular nucleus of the hypothalamus (PVN) showed that in saline treated rats, NK3R IR was largely membrane bound but following Senktide, NK3R IR was detected in punctate clusters within the cytoplasm within 10 min of the intraventricular injection. Interestingly, at 20 min, NK3R IR was detected within the cell nuclei. The presence of NK3R in the cell nuclei was confirmed by immunoelectron microscopy and Western blot. Thus, intraventricular injections of Senktide activate NK3R expressed by PVN neurons and causes the internalization and translocation of the NK3R to the cell nuclei, where the protein may directly affect gene transcription.
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Intraventricular injections of tachykinin NK3 receptor agonists suppress the intake of "salty" tastes by sodium deficient rats.
Behavioural brain research, 2005Co-Authors: Francis W. FlynnAbstract:Abstract Intraventricular injections of the tachykinin NK3 receptor (NK3-R) agonist, Senktide, suppress the ingestion of hypertonic (0.5 M) NaCl by decreasing the initial lick rate and accelerating the decay in lick rate in sodium deficient rats. The present experiment examined whether the effects of intraventricular injections of Senktide on lick rate were selective for NaCl solution, or if the ability of NK3-R agonists to inhibit intake generalizes other sodium-containing solutions. The effects of lateral ventricular injections of isotonic saline or Senktide (200 ng) on intake and lick rate of 0.5 M solutions of sodium chloride (NaCl), sodium acetate (Na acetate), sodium bicarbonate (Na bicarbonate), and monosodium glutamate (MSG) were measured in sodium deficient rats. Compared to saline injection, Senktide injection had no effect on the lick rate or intake of Na bicarbonate. In contrast, intraventricular injection of Senktide suppressed the intake of NaCl, Na acetate, and MSG compared to saline injection. Senktide injection accelerated the decay in lick rate for NaCl, Na acetate and MSG, but only suppressed the initial lick rate for NaCl and Na acetate. The results show that activation of NK3-R in sodium deficient rats suppresses the intake of tastes that are classified as “salty” tasting and that the decrease in intake reflects effects on the initial lick rate, the decay in lick rate, or both.
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Central neurokinin 3 receptors increase systemic oxytocin release: interaction with norepinephrine.
Experimental Neurology, 2003Co-Authors: Steven L. Bealer, Francis W. FlynnAbstract:Stimulation of central tachykinin receptors contributes to neuroendocrine functions of the hypothalamo-neurohypophyseal system. However, the specific role of each tachykinin receptor subtype has not been completely characterized. Specifically, while neurokinin 3 (NK3) receptor stimulation increases systemic vasopressin, the effects on oxytocin (OT) are not known. Therefore, the present studies investigated the effect of central NK3 receptor stimulation with Senktide on release of systemic and central OT. Furthermore, since central NK3 receptors activate noradrenergic systems, which contribute to OT release, the effects of α-adrenergic receptor blockade on Senktide-induced changes in OT release were evaluated. Female rats were implanted with a cannula in the third cerebral ventricle, and changes in plasma OT concentration determined before and following central administration of Senktide in vehicle-treated rats, and animals following central administration of the α-adrenergic antagonist phentolamine. Other rats were implanted with microdialysis probes adjacent to the paraventricular nucleus (PVN), and dialysate and plasma OT concentrations were determined before and during administration of Senktide through the dialysis probe. Central Senktide increased systemic OT release, which was prevented by pretreatment with phentolamine. Furthermore, there was no detectable change in extracellular OT concentration in the PVN during dialysis administration of Senktide. These data demonstrate that activation of central NK3 receptors stimulates systemic release of OT by activation of central noradrenergic systems, apparently without increasing intranuclear OT release in the PVN.
Maria A. De Souza Silva - One of the best experts on this subject based on the ideXlab platform.
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NK3 receptor agonism reinstates temporal order memory in the hemiparkinsonian rat
Behavioural brain research, 2014Co-Authors: Owen Y. Chao, Susanne Nikolaus, An-li Wang, Maria A. De Souza SilvaAbstract:Animals treated with unilateral 6-hydroxydopamine (6-ODHA) injections, an animal model of Parkinson's disease, exhibit deficits in memory for temporal order, but show intact novel object recognition. Since Senktide, a potent neurokinin-3 receptor (NK3-R) agonist, has been shown to have promnestic effects in the aged rat and to alleviate scopolamine-induced impairment, the present study aimed to assess possible promnestic effects of Senktide in the hemiparkinsonian rat model. Animals received unilateral 6-ODHA microinjections into the medial forebrain bundle. Two weeks later, they were randomly assigned to treatment with vehicle, 0.2, or 0.4 mg/kg Senktide. Temporal order memory and place recognition tests were conducted, locomotor activity and turning behavior were assessed in the open field and anxiety-related behavior was measured in the light-dark box. Treatments were administered 30 min prior to behavioral testing with an interval of seven days between tests. The animals treated with 0.2 mg/kg Senktide exhibited temporal order memory, unlike the vehicle-treated group. No significant treatment effects were found in the open field and light-dark box. Administration of 0.2 mg/kg Senktide may influence the prefrontal cortex and hippocampus, leading to compensations for deficits in memory for temporal order.
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The neurokinin-3 receptor agonist Senktide facilitates the integration of memories for object, place and temporal order into episodic memory.
Neurobiology of Learning and Memory, 2014Co-Authors: Owen Y. Chao, Susanne Nikolaus, Joseph P. Huston, Maria A. De Souza SilvaAbstract:Abstract Senktide, a potent neurokinin-3 receptor (NK3-R) agonist, has been shown to have promnestic effects in adult and aged rodents and to facilitate episodic-like memory (ELM) in mice when administrated before the learning trial. In the present study we assessed the effects of Senktide on memory consolidation by administering it post-trial (after the learning trial) in adult rats. We applied an ELM test, based on the integrated memory for object, place and temporal order, which we developed ( Kart-Teke, de Souza Silva, Huston, & Dere, 2006 ). This test involves two learning trials and one test trial. We examined intervals of 1 h and 23 h between the learning and test trials (experiment 1) in untreated animals and found that they exhibited intact ELM after a delay of 1 h, but not 23 h. In another test for ELM performed 7 days later, vehicle or Senktide (0.2 mg/kg, s.c.) was applied immediately after the second learning trial and the test was conducted 23 h later (experiment 2). Senktide treatment recovered components of ELM (memory for place and object) compared with vehicle-treated animals. After one more week, vehicle or Senktide (0.2 mg/kg, s.c.) was applied post-trial and the test conducted 6 h later (experiment 3). The Senktide-treated group exhibited intact ELM, unlike the vehicle-treated group. Finally, animals received post-trial treatment with either vehicle or SR142801, a selective NK3-R antagonist (6 mg/kg, i.p.), 1 min before Senktide injection (0.2 mg/kg, s.c.) in the ELM paradigm and were tested 6 h later (experiment 4). The vehicle + Senktide group showed intact ELM, while the SR142801 + Senktide group did not. The results indicate that Senktide facilitated the consolidation or the expression of ELM and that the Senktide effect was NK3-R dependent.
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The NK3 receptor agonist Senktide ameliorates scopolamine-induced deficits in memory for object, place and temporal order.
Neurobiology of learning and memory, 2011Co-Authors: Sandra Schäble, Joseph P. Huston, Marilia Barros, Carlos Tomaz, Maria A. De Souza SilvaAbstract:Senktide, a potent neurokinin-3 receptor (NK3-R) agonist, increases acetylcholine (ACh) release in the striatum, the prefrontal cortex (Schable et al., 2011), the amygdala and hippocampus, presumably via postsynaptic mechanisms. A promnestic action of NK3-R agonists has been described in a variety of learning/memory tasks. The memory-enhancing effects of NK3-R agonists and their activating influence on ACh suggest a possible role of the NK3-R in learning and memory via cholinergic modulation. Deterioration of the cholinergic system in the basal forebrain has been associated with learning and memory deficits and cholinergic agents have promnestic effects in a variety of learning paradigms. The anticholinergic drug, scopolamine, a muscarinic ACh receptor antagonist, incurs deficits in a variety of learning tasks and provides a useful tool to investigate the role of the cholinergic systems in mechanisms underlying learning and memory. The aim of this study was to ascertain the effect of the NK3-R agonist, Senktide, in the scopolamine-induced deficit model. We hypothesized that Senktide treatment would attenuate scopolamine-induced (subcutaneous--s.c. 0.75 mg/kg) memory impairment in three novelty preference paradigms based on spontaneous object exploration: namely object recognition, object-place recognition and object recognition for temporal order. Administration of Senktide reversed the scopolamine-induced memory deficits by re-establishing object recognition (s.c. 0.2 mg/kg), object-place recognition (0.2 and 0.4 mg/kg), as well as object recognition for temporal order (0.4 mg/kg) in adult Wistar rats. These results indicate memory enhancing effects of Senktide in animals subjected to scopolamine-induced memory impairments and indicate that the promnestic action of NK3-R agonists is mediated by muscarinic cholinergic mechanisms.
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NK3 receptor agonism promotes episodic-like memory in mice
Neurobiology of learning and memory, 2008Co-Authors: Armin Zlomuzica, Joseph P. Huston, Ekrem Dere, Maria A. De Souza SilvaAbstract:The mammalian tachykinins are a family of closely related peptides including substance P, neurokinin A, neurokinin B and, recently, also hemokinin-1. They are present in the peripheral and central nervous systems, and bind to three known neurokinin (NK) receptors, the NK(1)-, NK(2)- and NK(3) receptors. In both rodents and humans, NK(3) receptors are expressed in brain structures which have been associated with learning and memory. Evidence for a role of NK(3) receptors in learning and memory has been found in NK(3) receptor knockout mice. Here, we investigated the influence of the NK(3) receptor agonist, Senktide (0.1, 0.2 and 0.4 mg/kg), on the performance of C57BL/6 mice in a recently developed episodic-like memory task. Since a promnestic effect of Senktide was expected, we employed an experimental protocol that provided sub-optimal learning conditions for episodic-like memory. The results indicate that Senktide promotes episodic-like memory in mice in a dose-dependent manner, providing, for the first time, evidence for an involvement of NK(3) receptors in episodic-like memory.
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interaction of the tachykinin nk3 receptor agonist Senktide with behavioral effects of cocaine in marmosets callithrix penicillata
Peptides, 2006Co-Authors: Maria A. De Souza Silva, Joseph P. Huston, Gerhard Jocham, Christian P. Müller, Carlos Tomaz, Eldon L Mello, Rafael S Maior, Marilia BarrosAbstract:Brain neuropeptide transmitters of the tachykinin family are involved in the organization of many behaviors. However, little is known about their contribution to the behavioral effects of drugs of abuse. Recently, antagonism of the tachykinin NK3-receptor (NK3-R), one of the three tachykinin receptors in the brain, was shown to attenuate the acute and chronic behavioral effects of cocaine in rats and the acute effects in non-human primates. In order to expand these findings we investigated the effects of the NK3-R agonist, succinyl-[Asp6, Me-Phe8]SP(6-11) (Senktide), on the acute behavioral effects of cocaine in marmoset monkeys (Callithrix penicillata) using a figure-eight maze procedure. Animals were pretreated with Senktide (0, 0.1, 0.2, 0.4 mg/kg, s.c.), and received either a treatment with cocaine (10 mg/kg) or saline (i.p.). Cocaine increased locomotor activity and the duration of aerial scanning behavior, but reduced exploratory activity, bodycare activity, the frequency of aerial scanning, and terrestrial glance behavior. Senktide blocked the effects of cocaine on locomotor activity, but enhanced the cocaine effects on exploratory activity, aerial scanning frequency, and terrestrial glance behavior. Senktide alone did not significantly influence monkey behavior in this study. These data expand previous findings suggesting a complex role of the NK3-R in the acute behavioral effects of cocaine in non-human primates.
Hiro-o Kamiya - One of the best experts on this subject based on the ideXlab platform.
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Antidiuretic action of tachykinin NK-3 receptor in the rat paraventricular nucleus.
Brain Research, 1996Co-Authors: Takashi Eguchi, Yukio Takano, Ryo Saito, Yasuhisa Nakayama, Takashi Hatae, Yasufumi Shigeyoshi, Hitoshi Okamura, James E. Krause, Hiro-o KamiyaAbstract:Abstract Studies were performed on the central antidiuretic actions via the tachykinin NK-3 receptor in the rat hypothalamic paraventricular nucleus (PVN). Microinjections of the selective tachykinin NK-3 receptor agonist Senktide (2–200 pmol) into the PVN resulted in prolonged inhibition of urine output in water-loaded rats, its effect being dose-dependent. The antidiuretic action of Senktide was blocked by pretreatment with the vasopressin V2 receptor antagonist OPC-31260 (1 mg/kg, i.v.), but not by microinjection of the angiotensin II AT-1 receptor antagonist losartan (1 nmol) into the PVN. NK-3 receptor mRNA was strongly detected in the magnocellular part of the PVN and the supraoptic nucleus (SON) of the hypothalamus as detected by in situ hybridization histochemistry. Moreover, [3H]Senktide binding sites were also detected in the PVN and the SON by receptor autoradiography. These findings suggest that NK-3 receptors in the PVN may be involved in water regulation by stimulation of vasopressin secretion from the posterior pituitary gland, and that vasopressin caused water reabsorbtion via the kidney V2 receptor.
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Nitric oxide is a mediator of tachykinin NK3 receptor-induced relaxation in rat mesenteric artery
British journal of pharmacology, 1995Co-Authors: Aki Mizuta, Yukio Takano, Ryo Saito, Kenji Honda, Takafumi Matsumoto, Hiro-o KamiyaAbstract:1. The mechanism of vasodilatation induced by tachykinin peptides was studied in isolated mesenteric arteries of rats. 2. Senktide, a selective NK3 agonist, elicited potent endothelium-dependent relaxation of arteries precontracted with phenylephrine (10(-5) M), but an NK1 agonist did not. 3. A non-peptide NK3 antagonist, SR 142801, inhibited Senktide-induced relaxation. However, a non-peptide NK1 antagonist, CP-96,345, and a peptide-based NK2 antagonist, L-659,877, had no effect on Senktide-induced relaxation. 4. N omega-nitro-L-arginine (L-NOARG), a nitric oxide synthesis inhibitor, markedly attenuated the relaxant response to Senktide. 5. These results suggest that the endothelium of rat mesenteric arteries possesses tachykinin NK3 receptors, and that NK3 agonist-induced vasodilatation is mediated by release of nitric oxide (NO) from the endothelium.
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Central pressor actions of tachykinin NK-3 receptor in the paraventricular nucleus of the rat hypothalamus.
Brain research, 1992Co-Authors: Yasuhisa Nakayama, Yukio Takano, Ryo Saito, Hiro-o KamiyaAbstract:The central pressor actions of the tachykinin NK-3 receptor in the paraventricular nucleus (PVN) of the hypothalamus were examined in anesthetized rats. In forebrain-restricted animals, the selective tachykinin NK-3 receptor agonist Senktide (10 micrograms, i.c.v.) increased the blood pressure, and this pressor response was more potent than in control animals. Injection of Senktide into the PVN also increased the blood pressure, and this pressor response was inhibited by pretreatment with the vasopressin V1 receptor antagonist (10 micrograms/kg, i.v.). These results suggest that central injection of Senktide stimulated the NK-3 receptor in the PVN of the hypothalamus, and increased blood pressure by inducing release of vasopressin from the pituitary gland.
Giovanna Improta - One of the best experts on this subject based on the ideXlab platform.
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Selective tachykinin NK3-receptor agonists stimulate in vitro exocrine pancreatic secretion in the guinea pig
'Elsevier BV', 2002Co-Authors: G. Linari, Maria Broccardo, V Nucerito, Giovanna ImprotaAbstract:The tachykinins, including substance P, neurokinin A and neurokinin B, are a mammalian peptide family that have documented motor, sensory and circulatory neurotransmitter functions in the gut. Little is known about their action on the exocrine pancreas. In this study we investigated the effects of PG-KII, a natural NK3-tachykinin receptor agonist, and Senktide, a synthetic NK3-tachykinin receptor agonist, on amylase release from isolated pancreatic lobules of the guinea pig in comparison with the secretagogues carbachol, caerulein and substance P and the depolarizing agent KCl. When added to incubation flasks at various concentrations (from 10(-10) to 10(-6) M), PG-KII and senkfide both caused a dose-dependent increase in amylase release from pancreatic lobules. PG-KII and Senktide elicited a lower maximal response (7.5 +/- 0.8 and 8.1 +/- 0.6% of the total lobular amylase content) than carbachol (34.4 +/- 3.9%), caerulein (26.5 +/- 2.8%) and KCl (22.5 +/- 3.8%). Whereas atropine left PG-KII and Senktide-stimulated secretion unaffected, the non peptide NK3 receptor antagonist SR 142801 significantly reduced the stimulant effect of PG-KII and Senktide. PG-KII (10(-7) M) also slightly though significantly increased the response to lower concentrations of caerulein (10(-11) and 10(-10) M) and carbachol (10(-7) and 10(-6) M). These findings show that PG-KII and senkfide are weak stimulants of exocrine pancreatic secretion that act directly on the acinar cells through NK3 receptors, without cholinergic involvement. We suggest also that the tachykininergic NK3 receptor system cooperates with the other known secretagogues in the control of pancreatic exocrine secretion. (C) 2002 Elsevier Science Inc. All rights reserved
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Selective tachykinin NK3-receptor agonists stimulate in vitro exocrine pancreatic secretion in the guinea pig.
Peptides, 2002Co-Authors: G. Linari, Maria Broccardo, V Nucerito, Giovanna ImprotaAbstract:Abstract The tachykinins, including substance P, neurokinin A and neurokinin B, are a mammalian peptide family that have documented motor, sensory and circulatory neurotransmitter functions in the gut. Little is known about their action on the exocrine pancreas. In this study we investigated the effects of PG-KII, a natural NK 3 -tachykinin receptor agonist, and Senktide, a synthetic NK 3 -tachykinin receptor agonist, on amylase release from isolated pancreatic lobules of the guinea pig in comparison with the secretagogues carbachol, caerulein and substance P and the depolarizing agent KCl. When added to incubation flasks at various concentrations (from 10 −10 to 10 −6 M), PG-KII and Senktide both caused a dose-dependent increase in amylase release from pancreatic lobules. PG-KII and Senktide elicited a lower maximal response (7.5±0.8 and 8.1±0.6% of the total lobular amylase content) than carbachol (34.4±3.9%), caerulein (26.5±2.8%) and KCl (22.5±3.8%). Whereas atropine left PG-KII and Senktide-stimulated secretion unaffected, the non peptide NK 3 receptor antagonist SR 142801 significantly reduced the stimulant effect of PG-KII and Senktide. PG-KII (10 −7 M) also slightly though significantly increased the response to lower concentrations of caerulein (10 −11 and 10 −10 M) and carbachol (10 −7 and 10 −6 M). These findings show that PG-KII and Senktide are weak stimulants of exocrine pancreatic secretion that act directly on the acinar cells through NK 3 receptors, without cholinergic involvement. We suggest also that the tachykininergic NK 3 receptor system cooperates with the other known secretagogues in the control of pancreatic exocrine secretion.
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Inhibitory role on gastric secretion of a central NK-3 tachykinin receptor agonist, Senktide.
Peptides, 1991Co-Authors: Giovanna Improta, Maria BroccardoAbstract:When administered intracerebroventricularly, the highly selective NK-3 tachykinin receptor agonist Senktide possesses a potent and dose-related inhibitory effect on gastric acid secretion. The central mechanism governing the antisecretory effect of Senktide was examined in perfused-stomach rats by studying its influence on gastric acid secretion elicited by the secretagogues histamine, pentagastrin and bethanechol. Given intracerebroventricularly, Senktide reduced the acid response to histamine, but not that to pentagastrin or bethanechol. Stimulation of NK-3 receptors in rat brain thus appears to inhibit gastric acid secretion through histaminergic pathways.
Maria Broccardo - One of the best experts on this subject based on the ideXlab platform.
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Selective tachykinin NK3-receptor agonists stimulate in vitro exocrine pancreatic secretion in the guinea pig
'Elsevier BV', 2002Co-Authors: G. Linari, Maria Broccardo, V Nucerito, Giovanna ImprotaAbstract:The tachykinins, including substance P, neurokinin A and neurokinin B, are a mammalian peptide family that have documented motor, sensory and circulatory neurotransmitter functions in the gut. Little is known about their action on the exocrine pancreas. In this study we investigated the effects of PG-KII, a natural NK3-tachykinin receptor agonist, and Senktide, a synthetic NK3-tachykinin receptor agonist, on amylase release from isolated pancreatic lobules of the guinea pig in comparison with the secretagogues carbachol, caerulein and substance P and the depolarizing agent KCl. When added to incubation flasks at various concentrations (from 10(-10) to 10(-6) M), PG-KII and senkfide both caused a dose-dependent increase in amylase release from pancreatic lobules. PG-KII and Senktide elicited a lower maximal response (7.5 +/- 0.8 and 8.1 +/- 0.6% of the total lobular amylase content) than carbachol (34.4 +/- 3.9%), caerulein (26.5 +/- 2.8%) and KCl (22.5 +/- 3.8%). Whereas atropine left PG-KII and Senktide-stimulated secretion unaffected, the non peptide NK3 receptor antagonist SR 142801 significantly reduced the stimulant effect of PG-KII and Senktide. PG-KII (10(-7) M) also slightly though significantly increased the response to lower concentrations of caerulein (10(-11) and 10(-10) M) and carbachol (10(-7) and 10(-6) M). These findings show that PG-KII and senkfide are weak stimulants of exocrine pancreatic secretion that act directly on the acinar cells through NK3 receptors, without cholinergic involvement. We suggest also that the tachykininergic NK3 receptor system cooperates with the other known secretagogues in the control of pancreatic exocrine secretion. (C) 2002 Elsevier Science Inc. All rights reserved
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Selective tachykinin NK3-receptor agonists stimulate in vitro exocrine pancreatic secretion in the guinea pig.
Peptides, 2002Co-Authors: G. Linari, Maria Broccardo, V Nucerito, Giovanna ImprotaAbstract:Abstract The tachykinins, including substance P, neurokinin A and neurokinin B, are a mammalian peptide family that have documented motor, sensory and circulatory neurotransmitter functions in the gut. Little is known about their action on the exocrine pancreas. In this study we investigated the effects of PG-KII, a natural NK 3 -tachykinin receptor agonist, and Senktide, a synthetic NK 3 -tachykinin receptor agonist, on amylase release from isolated pancreatic lobules of the guinea pig in comparison with the secretagogues carbachol, caerulein and substance P and the depolarizing agent KCl. When added to incubation flasks at various concentrations (from 10 −10 to 10 −6 M), PG-KII and Senktide both caused a dose-dependent increase in amylase release from pancreatic lobules. PG-KII and Senktide elicited a lower maximal response (7.5±0.8 and 8.1±0.6% of the total lobular amylase content) than carbachol (34.4±3.9%), caerulein (26.5±2.8%) and KCl (22.5±3.8%). Whereas atropine left PG-KII and Senktide-stimulated secretion unaffected, the non peptide NK 3 receptor antagonist SR 142801 significantly reduced the stimulant effect of PG-KII and Senktide. PG-KII (10 −7 M) also slightly though significantly increased the response to lower concentrations of caerulein (10 −11 and 10 −10 M) and carbachol (10 −7 and 10 −6 M). These findings show that PG-KII and Senktide are weak stimulants of exocrine pancreatic secretion that act directly on the acinar cells through NK 3 receptors, without cholinergic involvement. We suggest also that the tachykininergic NK 3 receptor system cooperates with the other known secretagogues in the control of pancreatic exocrine secretion.
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Inhibitory role on gastric secretion of a central NK-3 tachykinin receptor agonist, Senktide.
Peptides, 1991Co-Authors: Giovanna Improta, Maria BroccardoAbstract:When administered intracerebroventricularly, the highly selective NK-3 tachykinin receptor agonist Senktide possesses a potent and dose-related inhibitory effect on gastric acid secretion. The central mechanism governing the antisecretory effect of Senktide was examined in perfused-stomach rats by studying its influence on gastric acid secretion elicited by the secretagogues histamine, pentagastrin and bethanechol. Given intracerebroventricularly, Senktide reduced the acid response to histamine, but not that to pentagastrin or bethanechol. Stimulation of NK-3 receptors in rat brain thus appears to inhibit gastric acid secretion through histaminergic pathways.
