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Pushpa S. Kalra - One of the best experts on this subject based on the ideXlab platform.
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the hypothalamic peptides beta endorphin Neuropeptide K and interleuKin 1 beta and the opiate morphine enhance the excitatory amino acid induced lh release under the influence of gonadal steroids
Journal of Neuroendocrinology, 1994Co-Authors: J J Bonavera, Abhiram Sahu, Satya P. Kalra, Pushpa S. KalraAbstract:Several hypothalamic Neuropeptides and amino acids are Known to inhibit or excite pituitary luteinizing hormone (LH) release, but the precise interplay between these 2 classes of signals in episodic LH discharge is not Known. In this study, we have evaluated the interaction between Neuropeptides shown previously to inhibit LH release in castrated rats and the excitatory amino acid agonist, N-methyl-D-aspartate (NMDA), on LH release in intact male rats. Rats received a permanent intracerebroventricular (i.c.v.) cannula and 9–12 days later an intrajugular cannula for frequent blood sampling. The next day, rats received i.c.v. either saline (SAL, 3 μl, controls) or a Neuropeptide: the opioid β-endorphin (β-END; 2.9 nmol), the tachyKinin Neuropeptide K (NPK, 2.5 nmol) or the cytoKine interleuKin-1β (IL-1β, 5.9 pmol) in SAL. The LH response to 2 consecutive i.v. injections of NMDA (5 mg/Kg) at 30 min intervals was evaluated. In control rats, each NMDA injection evoKed a significant release of LH at 10 min. Quite unexpectedly, the three peptides, instead of exerting an inhibitory effect, enhanced the LH response to NMDA. The peaK plasma LH levels after each NMDA injection and the cumulative LH responses were significantly higher in peptide-treated than in control rats. This peculiar ability of the peptides that inhibit LH release in castrated rats, to potentiate the NMDA-induced LH release in the presence of gonadal steroids was further validated in female rats treated with an opiate receptor agonist, morphine (MOR) which is also Known to suppress LH release in ovariectomized rats. Rats were ovariectomized (ovx) and 14 days later received one estradiol-17β-containing Silastic® capsule s.c. (E2, 300 μg/ml oil). In addition, each rat received 1 pellet of placebo (PLA, control) or MOR (75 mg/pellet) s.c. followed 2 days later by 2 additional PLA or MOR pellets, and an intrajugular cannula. The LH response of these rats to 2 i.v. injections of NMDA (5 mg/Kg) 30 min apart was evaluated. The results showed that each injection of NMDA elicited a pulse of LH with peaK levels at 10 min in control rats. However, in MOR-treated rats the LH response to NMDA was amplified; peaK and cumulative LH responses were significantly higher in these rats. To ascertain whether this augmentation of LH response induced by MOR was exerted at the hypothalamic level, the effects of NMDA on in vitro LHRH release from the median eminence-arcuate nucleus (ME-ARC) fragment of ovx rats similarly pretreated with E2 and PLA or MOR were compared. The results showed that LHRH efflux in response to 50 mM NMDA alone and in combination with 23 mM KCl was higher in MOR-treated than in control rats. Cumulatively, these results show that activation of hypothalamic opioid, tachyKinin and cytoKine receptors which ordinarily result in suppression of LH release in gonadal steroid deficient rats, concurrently enhances the excitatory LH response of NMDA under the influence of gonadal steroids. These unexpected findings reveal a novel modality of involvement of these peptides in the hypothalamic control of pituitary LH release. While these peptides may play a role in attenuating LH secretion in intact rats, our studies are in accord with the view that these peptides enhance the response of the hypothalamo-pituitary axis to incoming signals, including the excitatory amino acids, that excite the release of LH.
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evidence that luteinizing hormone suppression in response to inhibitory Neuropeptides beta endorphin interleuKin 1 beta and Neuropeptide K may involve excitatory amino acids
Endocrinology, 1993Co-Authors: J J Bonavera, Satya P. Kalra, Pushpa S. KalraAbstract:A large body of recent evidence suggests that a number of inhibitory and excitatory Neuropeptides and amino acids may participate in the episodic secretion of hypothalamic LHRH and pituitary LH in castrated rats. However, the precise functional relationships among these messenger molecules in the control of LH secretion remain to be ascertained. The aim of this study was to test the hypothesis that inhibition of LH release by an opioid [beta-endorphin (beta END)], cytoKine [interleuKin-1 beta (IL-1 beta)], or tachyKinin [Neuropeptide-K (NPK)] is a result of diminished excitatory amino acid (EAA) signaling. Adult male rats were castrated and received an intracerebroventricular cannula in the third ventricle for administration of beta END (10 micrograms/rat), NPK (2.5 nmol/rat), or IL-1 beta (100 ng/rat) 2 weeKs postcastration. One day before the experiments, rats received an intraatrial cannula for frequent blood sampling and for iv injection of the glutamate receptor agonist N-methyl-D-aspartate (NMDA; 5 ...
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Neuropeptide K stimulates corticosterone release in the rat
Brain research, 1993Co-Authors: Pushpa S. Kalra, Satya P. KalraAbstract:Abstract We have investigated the effects of the tachyKinin, neuroKinin A (NKA) and the N-terminally extended forms NPK and NPγ on plasma levels of corticosterone. Both peripheral and central injections of these three NK-2 receptor agonists stimulated adrenal corticosterone release in gonad-intact and castrated male rats. A comparison of their effects revealed that NPK was relatively more potent than NKA and NPγ. These results suggest that tachyKinins may act at both central and peripheral sites to stimulate corticosterone release and that NKA and NPγ may represent degradation forms of the larger, biologically effective tachyKinin, NPK.
Satya P. Kalra - One of the best experts on this subject based on the ideXlab platform.
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the hypothalamic peptides beta endorphin Neuropeptide K and interleuKin 1 beta and the opiate morphine enhance the excitatory amino acid induced lh release under the influence of gonadal steroids
Journal of Neuroendocrinology, 1994Co-Authors: J J Bonavera, Abhiram Sahu, Satya P. Kalra, Pushpa S. KalraAbstract:Several hypothalamic Neuropeptides and amino acids are Known to inhibit or excite pituitary luteinizing hormone (LH) release, but the precise interplay between these 2 classes of signals in episodic LH discharge is not Known. In this study, we have evaluated the interaction between Neuropeptides shown previously to inhibit LH release in castrated rats and the excitatory amino acid agonist, N-methyl-D-aspartate (NMDA), on LH release in intact male rats. Rats received a permanent intracerebroventricular (i.c.v.) cannula and 9–12 days later an intrajugular cannula for frequent blood sampling. The next day, rats received i.c.v. either saline (SAL, 3 μl, controls) or a Neuropeptide: the opioid β-endorphin (β-END; 2.9 nmol), the tachyKinin Neuropeptide K (NPK, 2.5 nmol) or the cytoKine interleuKin-1β (IL-1β, 5.9 pmol) in SAL. The LH response to 2 consecutive i.v. injections of NMDA (5 mg/Kg) at 30 min intervals was evaluated. In control rats, each NMDA injection evoKed a significant release of LH at 10 min. Quite unexpectedly, the three peptides, instead of exerting an inhibitory effect, enhanced the LH response to NMDA. The peaK plasma LH levels after each NMDA injection and the cumulative LH responses were significantly higher in peptide-treated than in control rats. This peculiar ability of the peptides that inhibit LH release in castrated rats, to potentiate the NMDA-induced LH release in the presence of gonadal steroids was further validated in female rats treated with an opiate receptor agonist, morphine (MOR) which is also Known to suppress LH release in ovariectomized rats. Rats were ovariectomized (ovx) and 14 days later received one estradiol-17β-containing Silastic® capsule s.c. (E2, 300 μg/ml oil). In addition, each rat received 1 pellet of placebo (PLA, control) or MOR (75 mg/pellet) s.c. followed 2 days later by 2 additional PLA or MOR pellets, and an intrajugular cannula. The LH response of these rats to 2 i.v. injections of NMDA (5 mg/Kg) 30 min apart was evaluated. The results showed that each injection of NMDA elicited a pulse of LH with peaK levels at 10 min in control rats. However, in MOR-treated rats the LH response to NMDA was amplified; peaK and cumulative LH responses were significantly higher in these rats. To ascertain whether this augmentation of LH response induced by MOR was exerted at the hypothalamic level, the effects of NMDA on in vitro LHRH release from the median eminence-arcuate nucleus (ME-ARC) fragment of ovx rats similarly pretreated with E2 and PLA or MOR were compared. The results showed that LHRH efflux in response to 50 mM NMDA alone and in combination with 23 mM KCl was higher in MOR-treated than in control rats. Cumulatively, these results show that activation of hypothalamic opioid, tachyKinin and cytoKine receptors which ordinarily result in suppression of LH release in gonadal steroid deficient rats, concurrently enhances the excitatory LH response of NMDA under the influence of gonadal steroids. These unexpected findings reveal a novel modality of involvement of these peptides in the hypothalamic control of pituitary LH release. While these peptides may play a role in attenuating LH secretion in intact rats, our studies are in accord with the view that these peptides enhance the response of the hypothalamo-pituitary axis to incoming signals, including the excitatory amino acids, that excite the release of LH.
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evidence that luteinizing hormone suppression in response to inhibitory Neuropeptides beta endorphin interleuKin 1 beta and Neuropeptide K may involve excitatory amino acids
Endocrinology, 1993Co-Authors: J J Bonavera, Satya P. Kalra, Pushpa S. KalraAbstract:A large body of recent evidence suggests that a number of inhibitory and excitatory Neuropeptides and amino acids may participate in the episodic secretion of hypothalamic LHRH and pituitary LH in castrated rats. However, the precise functional relationships among these messenger molecules in the control of LH secretion remain to be ascertained. The aim of this study was to test the hypothesis that inhibition of LH release by an opioid [beta-endorphin (beta END)], cytoKine [interleuKin-1 beta (IL-1 beta)], or tachyKinin [Neuropeptide-K (NPK)] is a result of diminished excitatory amino acid (EAA) signaling. Adult male rats were castrated and received an intracerebroventricular cannula in the third ventricle for administration of beta END (10 micrograms/rat), NPK (2.5 nmol/rat), or IL-1 beta (100 ng/rat) 2 weeKs postcastration. One day before the experiments, rats received an intraatrial cannula for frequent blood sampling and for iv injection of the glutamate receptor agonist N-methyl-D-aspartate (NMDA; 5 ...
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Neuropeptide K stimulates corticosterone release in the rat
Brain research, 1993Co-Authors: Pushpa S. Kalra, Satya P. KalraAbstract:Abstract We have investigated the effects of the tachyKinin, neuroKinin A (NKA) and the N-terminally extended forms NPK and NPγ on plasma levels of corticosterone. Both peripheral and central injections of these three NK-2 receptor agonists stimulated adrenal corticosterone release in gonad-intact and castrated male rats. A comparison of their effects revealed that NPK was relatively more potent than NKA and NPγ. These results suggest that tachyKinins may act at both central and peripheral sites to stimulate corticosterone release and that NKA and NPγ may represent degradation forms of the larger, biologically effective tachyKinin, NPK.
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Effects of tachyKinins on luteinizing hormone release in female rats: potent inhibitory action of Neuropeptide K.
Endocrinology, 1992Co-Authors: Abhiram Sahu, Satya P. KalraAbstract:TachyKinins, a family of biologically active related peptides, are found in variable amounts in the rat hypothalamus. We assessed the effects of five tachyKinins, substance P (SP), neuroKinin A (NKA), Neuropeptide K (NPK), Neuropeptide gamma (NP gamma), and neuroKinin B (NKB), on LH release in different experimental model systems in ovariectomized rats. In the first series of experiments rats were ovariectomized and implanted with permanent cannulae in the third cerebroventricle of the rat brain. Two weeKs later, the effects of intracerebroventricular injection of 0.5 or 1.25 nm various tachyKinins on LH release were studied. The results showed that whereas SP, NKA, and NKB were ineffective, and NP gamma was marginally effective, NPK produced a long-lasting suppression of LH release. NPK decreased LH release in a dose- and time-related fashion. Similarly, in the second series of experiments, whereas SP and NKA were inactive, NPK completely suppressed the LH surge induced by progesterone in estrogen-primed...
Luciano Debeljuk - One of the best experts on this subject based on the ideXlab platform.
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Development of a specific radioimmunoassay for Neuropeptide K: Its application to Siberian hamster tissues
Peptides, 1999Co-Authors: Luciano Debeljuk, Andrzej BartkeAbstract:Abstract In this report we describe the development of a radioimmunoassay for Neuropeptide K (NPK) that is not influenced by the presence of free neuroKinin A (NKA) or Neuropeptide γ (NPG). The antisera for the radioimmunoassay were obtained by immunizing rabbits with β-preprotachyKinin A fragment 69–91. This fragment contains the sequence 1–20 of NPK and has only the sequence 18–20 (Gly-His-Gly) in common with NPG. Two antisera were obtained, neither cross-reacting with NKA or NPG. The specificity of these antisera was confirmed by the finding of a major immunoreactive peaK in the eluates obtained from HPLC separation, corresponding to NPK. This radioimmunoassay was applied to the determination of NPK in hypothalamic and anterior pituitary extracts from Siberian hamsters. Hypothalami from male and female hamsters contained similar concentrations of NPK, although slightly higher in males. NPK levels in the hypothalamus of female Siberian hamsters showed few fluctuations during the estrous cycle, with the levels measured at estrus being significantly lower than at proestrus, diestrus I, and diestrus II. In anterior pituitaries from Siberian hamsters the concentrations of NPK were significantly lower in females than in males. This radioimmunoassay has demonstrated the presence of NPK in the anterior pituitary gland of the Siberian hamster, and it should be very useful for future studies on mechanisms of regulation of NPK secretion in different tissues.
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modulation of the hypothalamo pituitary gonadal axis and the pineal gland by neuroKinin a Neuropeptide K and Neuropeptide γ
Peptides, 1999Co-Authors: Luciano Debeljuk, Mercedes LasagaAbstract:Modulation of the hypothalamo-pituitary-gonadal axis and the pineal gland by neuroKinin A, Neuropeptide K, and Neuropeptide gamma. PEPTIDES 1999. NeuroKinin A (NKA), Neuropeptide K (NPK) and Neuropeptide gamma (NPG) are members of the family of tachyKinins, and act preferentially on NK-2 tachyKinin receptors. These peptides are widely distributed and are potent stimulators of smooth muscle contraction, especially in the respiratory and gastrointestinal tract. They also induce vasodilatation and plasma extravasation. Through their effects on the vascular tone, they are also potential regulators of the blood flow and therefore of the function of many organs and tissues. TachyKinins have been demonstrated to influence the secretory activity of endocrine cells, and they may have a physiological role as regulators of endocrine functions. A number of reports have indicated that NPK, NKA and NPG act on the hypothalamo-pituitary gonadal axis to regulate functions related to reproduction. Therefore, we thought that, at this point, it was important to review the available evidence suggesting the role of these tachyKinins on reproductive functions by effects exerted at 3 different levels of regulation: the hypothalamus, the anterior pituitary and the gonads. These 3 tachyKinin peptides were reported to have effects on reproductive functions, acting on the control of the secretion of gonadotropin and prolactin at the level of the hypothalamo-pituitary axis, and on the steroid secretion by the testes and the ovaries. Acting on the hypothalamus, tachyKinins, mainly NPK, were reported to inhibit LH secretion, but this effect is dependent on the presence of gonadal steroids. On the anterior pituitary gland, however, tachyKinins were shown to stimulate LH and prolactin secretion, and this effect is also dependent on the presence of gonadal steroids. TachyKinin concentrations in the hypothalamus and pituitary are regulated by steroid hormones. In the hypothalamus, estrogens and testosterone increase tachyKinin concentration. In the anterior pituitary gland, estradiol and thyroid hormones marKedly depress tachyKinin concentrations. Ovariectomy and exposure to short photoperiods significantly increase anterior pituitary tachyKinins in the Siberian hamster. In the pineal gland, SP and NK-1 receptors are present and, more recently, the presence of NKA and probably also NPK was demonstrated. Castration and steroid replacement modified the content of tachyKinins in the pineal gland. The removal of the superior cervical ganglia was followed by an increase in NKA content in the pineal gland. These results suggest that gonadal steroids may influence tachyKinins in the pineal gland. In the gonads, tachyKinins stimulated the secretory activity of Sertoli cells, but inhibited testosterone secretion by Leydig cells. There are very few reports on the role of tachyKinins in the ovary, but some of them indicated that these peptides are present in some of the ovarian structures, and they may affect the secretion of ovarian steroids. Thus, NKA, NPK and NPG appear to have a modulatory role, mainly acting as paracrine factors, on the hypothalamo-pituitary-gonadal axis.
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In vivo and in vitro effects of Neuropeptide K and Neuropeptide gamma on the release of growth hormone.
Neuroreport, 1995Co-Authors: Luciano Debeljuk, Andrzej Bartke, Valeria Rettori, Samuel M. MccannAbstract:There is anatomical and experimental evidence suggesting that tachyKinins have a role in the regulation of secretion of anterior pituitary hormones. In this investigation, the effects of Neuropeptide K and Neuropeptide gamma on the secretion of GH were studied in vivo and in vitro. Injections of Neuropeptide K into the third ventricle of freely moving, ovariectomized rats resulted in a significant increase of plasma GH, but Neuropeptide gamma induced no significant changes in these levels, although it did induce a significant increase in GH pulse height. In vitro, neither Neuropeptide K nor Neuropeptide gamma had any apparent effect on GH release from hemipituitaries incubated for 2 h. These results suggest that Neuropeptide K may have a modulatory function in the regulation of GH secretion from the anterior pituitary, through an action exerted at the hypothalamic level, and the effects of Neuropeptide gamma seem to be more marginal.
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tachyKinins and their gene expression in the anterior pituitary of the siberian hamster effects of photoperiod thyroid hormones and analogs of hypothalamic hormones
Endocrine, 1995Co-Authors: Luciano Debeljuk, Andrzej BartkeAbstract:The anterior pituitary gland of the Siberian hamster contains high concentrations of tachyKinins compared to other laboratory rodents. In this investigation we studied the relative quantities of neuroKinin A (NKA), Neuropeptide gamma (NPG), and Neuropeptide K (NPK) present in extracts of anterior pituitaries from this species. The anterior pituitary extracts, purified by HPLC, contained similar quantities of NKA and NPG, and lower quantities of NPK. The anterior pituitary gland of the Siberian hamster contained mRNA encoding β-preprotachyKinin A, which is a precursor of substance P, NKA, and NPK. This fact proves that the anterior pituitary gland of the Siberian hamster has the ability to synthesize tachyKinins. Animals exposed to short photoperiods had higher concentrations of tachyKinins in the pituitary gland, and triiodothyronine marKedly depressed the stores of these peptides in the anterior pituitary. In some groups of animals, the somatostatin analog octreotide induced a small, but significant decrease of the levels of NKA in the pituitary. The present results, together with previously published findings, indicate that thyroid hormones and estrogens are the most active endogenous substances to suppress the levels of anterior pituitary tachyKinins in the Siberian hamster.
Andrzej Bartke - One of the best experts on this subject based on the ideXlab platform.
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Development of a specific radioimmunoassay for Neuropeptide K: Its application to Siberian hamster tissues
Peptides, 1999Co-Authors: Luciano Debeljuk, Andrzej BartkeAbstract:Abstract In this report we describe the development of a radioimmunoassay for Neuropeptide K (NPK) that is not influenced by the presence of free neuroKinin A (NKA) or Neuropeptide γ (NPG). The antisera for the radioimmunoassay were obtained by immunizing rabbits with β-preprotachyKinin A fragment 69–91. This fragment contains the sequence 1–20 of NPK and has only the sequence 18–20 (Gly-His-Gly) in common with NPG. Two antisera were obtained, neither cross-reacting with NKA or NPG. The specificity of these antisera was confirmed by the finding of a major immunoreactive peaK in the eluates obtained from HPLC separation, corresponding to NPK. This radioimmunoassay was applied to the determination of NPK in hypothalamic and anterior pituitary extracts from Siberian hamsters. Hypothalami from male and female hamsters contained similar concentrations of NPK, although slightly higher in males. NPK levels in the hypothalamus of female Siberian hamsters showed few fluctuations during the estrous cycle, with the levels measured at estrus being significantly lower than at proestrus, diestrus I, and diestrus II. In anterior pituitaries from Siberian hamsters the concentrations of NPK were significantly lower in females than in males. This radioimmunoassay has demonstrated the presence of NPK in the anterior pituitary gland of the Siberian hamster, and it should be very useful for future studies on mechanisms of regulation of NPK secretion in different tissues.
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In vivo and in vitro effects of Neuropeptide K and Neuropeptide gamma on the release of growth hormone.
Neuroreport, 1995Co-Authors: Luciano Debeljuk, Andrzej Bartke, Valeria Rettori, Samuel M. MccannAbstract:There is anatomical and experimental evidence suggesting that tachyKinins have a role in the regulation of secretion of anterior pituitary hormones. In this investigation, the effects of Neuropeptide K and Neuropeptide gamma on the secretion of GH were studied in vivo and in vitro. Injections of Neuropeptide K into the third ventricle of freely moving, ovariectomized rats resulted in a significant increase of plasma GH, but Neuropeptide gamma induced no significant changes in these levels, although it did induce a significant increase in GH pulse height. In vitro, neither Neuropeptide K nor Neuropeptide gamma had any apparent effect on GH release from hemipituitaries incubated for 2 h. These results suggest that Neuropeptide K may have a modulatory function in the regulation of GH secretion from the anterior pituitary, through an action exerted at the hypothalamic level, and the effects of Neuropeptide gamma seem to be more marginal.
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tachyKinins and their gene expression in the anterior pituitary of the siberian hamster effects of photoperiod thyroid hormones and analogs of hypothalamic hormones
Endocrine, 1995Co-Authors: Luciano Debeljuk, Andrzej BartkeAbstract:The anterior pituitary gland of the Siberian hamster contains high concentrations of tachyKinins compared to other laboratory rodents. In this investigation we studied the relative quantities of neuroKinin A (NKA), Neuropeptide gamma (NPG), and Neuropeptide K (NPK) present in extracts of anterior pituitaries from this species. The anterior pituitary extracts, purified by HPLC, contained similar quantities of NKA and NPG, and lower quantities of NPK. The anterior pituitary gland of the Siberian hamster contained mRNA encoding β-preprotachyKinin A, which is a precursor of substance P, NKA, and NPK. This fact proves that the anterior pituitary gland of the Siberian hamster has the ability to synthesize tachyKinins. Animals exposed to short photoperiods had higher concentrations of tachyKinins in the pituitary gland, and triiodothyronine marKedly depressed the stores of these peptides in the anterior pituitary. In some groups of animals, the somatostatin analog octreotide induced a small, but significant decrease of the levels of NKA in the pituitary. The present results, together with previously published findings, indicate that thyroid hormones and estrogens are the most active endogenous substances to suppress the levels of anterior pituitary tachyKinins in the Siberian hamster.
Rejean Couture - One of the best experts on this subject based on the ideXlab platform.
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cardiovascular and behavioural effects of centrally administered Neuropeptide K in the rat receptor characterization
British Journal of Pharmacology, 1994Co-Authors: Alexandre Prat, Pierre Picard, Rejean CoutureAbstract:Abstract 1. The cardiovascular and behavioural responses to intracerebroventricularly (i.c.v.) administered Neuropeptide K (NPK) were studied in conscious rats. The central effects of NPK were characterized by pretreatment (i.c.v.) with selective antagonists for the NK1 ((+/-)-CP 96345 and RP 67580), NK2 (SR 48968) and NK3 (R 487) receptors. 2. NPK (10-65 pmol) induced tachycardia and dose-dependent increases of mean arterial blood pressure. The cardiovascular responses reached a maximum within 3 min post-injection and lasted for more than 1 h. Concurrently, NPK produced dose-dependent increases of face washing, head scratching, grooming, walKing and wet dog shaKes. 3. A desensitization of most of the behavioural responses (except head scratching) but not of the cardiovascular response was shown when two consecutive injections of 25 pmol NPK were given 24 h apart. 4. Both the cardiovascular and behavioural responses (except the head scratching) to 25 pmol NPK were blocKed by pre-administration (i.c.v.) of 6.5 nmol (+/-)-CP 96345 or RP 67580 given 5 min earlier. No inhibition of NPK responses was observed when 6.5 nmol SR 48968 or R 487 were used in a similar study. Additionally, NPK effects were significantly reduced 24 h after the prior injection of (+/-)-CP 96345 but not of RP 67580. 5. These results support the involvement of NK1 receptors in the cardiovascular and behavioural effects of i.c.v. NPK. Thus, this peptide may play a putative role in central cardiovascular regulation as it is the most potent endogenous tachyKinin described centrally, to date.
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Neuropeptide K potently stimulates the hydrolysis of phosphatidylinositol in the rat spinal cord
Neuroscience Letters, 1993Co-Authors: Alexandre Prat, Haroutioun M Hassessian, Rejean CoutureAbstract:Abstract The accumulation of total [3H]inositol phosphates stimulated by Neuropeptide K was investigated in rat spinal cord slices and compared with that of substance P and carbachol. The ranK order of potency of the agonists in stimulating [3H]phosphatidylinositol (PI) hydrolysis was Neuropeptide K > substance P > carbachol. The PI responses to Neuropeptide K and substance P were significantly (P
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cardiovascular and sympathoadrenal responses to intrathecal injection of Neuropeptide K in the conscious rat
Naunyn-schmiedebergs Archives of Pharmacology, 1993Co-Authors: T M Pham, De Champlain J, Rejean CoutureAbstract:In the conscious freely moving rat, the intrathecal (i.t.) injection of Neuropeptide K (NPK; 0.65 to 6.5 nmol), at T-9 spinal cord level, produced dose-dependent and prolonged (> 3 h) increases in mean arterial blood pressure (MAP) and heart rate (HR). The cardiovascular response to 3.25 nmol NPK was less sustained when injected at T-2 level. The cardiovascular response to 3.25 nmol NPK (T-9 level) was correlated with increases in plasma levels of noradrenaline, adrenaline and Neuropeptide Y (NPY), and was significantly reduced by the prior i.v. administration of inhibitors of either α-adrenoceptors (1 mg/Kg, phentolamine), α1-adrenoceptors (1 mg/Kg, prazosin), β1-adrenoceptors (1 mg/Kg, metoprolol) or angiotensin converting enzyme (10 mg/Kg, captopril). The cardiovascular response to NPK was also significantly reduced in rats that had undergone, 48 h earlier, bilateral adrenalectomy or to a greater extent sympathectomy with 6-hydroxydopamine. Whereas NPK-induced release of adrenaline was abolished by adrenalectomy, that of Neuropeptide Y and noradrenaline was blunted by either treatment. The results suggest that the cardiovascular effect of i.t. NPK is mediated by the stimulation of the sympathoadrenal system and the release of angiotensin. Sympathetic fibers may play a greater role than the adrenal medulla in the cardiovascular response to NPK. It appears that Neuropeptide Y derives from both sympathetic fibers and adrenal medullae. Hence, if released in the spinal cord, NPK may play an important role in cardiovascular and sympathoadrenal regulation.
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inhibitory action of cp 96 345 on the cardiovascular responses to intrathecal substance p and Neuropeptide K in the conscious freely moving rat
Naunyn-schmiedebergs Archives of Pharmacology, 1993Co-Authors: T M Pham, Rejean CoutureAbstract:(±)CP-96,345, a nonpeptide and highly selective NK-1 receptor antagonist, was tested acutely and chronically as an inhibitor of the cardiovascular responses induced by the intrathecal (i.t.) injection of substance P (SP) and Neuropeptide K (NPK) in the conscious rat. When given at T-9 spinal cord level, NPK (0.65, 3.25 and 6.5 nmol) and SP (6.5, 16.25 and 32.5 nmol) produced increases in mean arterial pressure and heart rate. The cardiovascular responses to NPK were greater in intensity and duration than those produced by SP. The prior i.t. injection of (±)CP-96,345 (0.65 and 6.5 nmol, 15 min earlier) inhibited in a dose-dependent manner the pressor response and the tachycardia induced by 6.5 nmol SP while 65 nmol of the antagonist was required to reduce the effects of 3.25 nmol NPK. However, both the SP and NPK-induced cardiovascular changes were blocKed 2 days after the Lt. injection of 6.5 nmol (±)CP-96,345. Five days after a single i.t. injection of 6.5 nmol (±)CP-96,345, the cardiovascular response to SP remained unaffected while that of NPK was partially attenuated. Moreover, (±)CP-96,345 was active as an antagonist when given ix. at the dose of 0.13 mg/Kg. Conversely, (±)CP-96,345 failed to blocK the cardiovascular effect caused by the i.t. injection of 81 pmol bradyKinin and did not produce any changes on resting blood pressure and heart rate when given alone either i.t. or L v. The results indicate that (±)CP-96,345 is a specific and long-acting antagonist which crosses the blood-brain barrier to blocK the action of SP and NPK in the spinal cord. Furthermore, these findings are consistent with the hypothesis that receptors of the NK-1 subtype mediate the cardiovascular responses evoKed by the spinal action of neuroKinins.
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characterization of the peripheral action of Neuropeptide K on the rat cardiovascular system
European Journal of Pharmacology, 1992Co-Authors: Anick Decarie, Rejean CoutureAbstract:The effects of Neuropeptide K (NPK) were measured on mean arterial pressure (MAP) and heart rate (HR) after i.v. injection in urethane-anesthetized rats. NPK (6.5 and 32.5 nmol/Kg) produced sustained decreases in MAP and elicited increases in HR. Whereas the NPK-induced tachycardia lasted more than 30 min at 32.5 nmol/Kg, a latent and long-lasting bradycardia appeared from 20 min after injection of 6.5 nmol/Kg. The initial tachycardia was converted to bradycardia by metoprolol but remained unaffected by hexamethonium, atropine and naloxone. These four treatments, however, prevented the bradycardiac response to NPK at 30 min. Whereas phentolamine, idazoxan, bilateral adrenalectomy and chemical sympathectomy with 6-hydroxydopamine (6-OHDA) preserved the initial tachycardia induced by NPK, they converted the decrease in HR to a tachycardiac response at 30 min. The vasodepressor response to NPK was significantly enhanced by bilateral adrenalectomy, chemical sympathectomy and metoprolol but remained unaffected by all other treatments. Neither the MAP nor the HR responses to NPK were affected by indomethacin. These results suggest that NPK can accelerate HR through non-reflex activation of the sympathoadrenal system. The secondary bradycardia induced by NPK may be due to a vagal reflex while the vasodepressor response to NPK is probably attributable to a direct action mediated by specific receptors on arterial blood vessels. Thus, NPK is considered as the most potent biologically active tachyKinin so far described on the rat cardiovascular system.