Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was undertaken to investigate the in vitro and in vivo pharmacological profile of the novel, nonpeptide neuropeptide Y (NPY) Y1-selective antagonist, BIBP 3226 [(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine-am ide], and a recently described peptidic structure [Ile-Glu-Pro-Orn-Tyr-Arg-Leu-Arg-Tyr-NH2, cyclic (2,4'), (2',4)-diamide]. BIBP 3226 antagonized the NPY Y1 receptor-mediated decrease in the twitch response in the rabbit vas deferens preparation with a pKb value of 6.98 +/- 0.06 (n = 16). It showed no affinity (EC50 > 1 microM) for NPY Y2 receptors in the rat vas deferens. NPY-induced increases in perfusion pressure in the isolated perfused rat kidney and rabbit ear preparations were antagonized with IC50 values of 26.8 +/- 4.5 (n = 4) and 214 +/- 30 nM (n = 4), respectively. The NPY-mediated potentiation of the noradrenaline elicited increase in perfusion pressure in the rat mesenteric bed was antagonized with an IC50 value of 976 (542-1760) nM. The NPY-induced increase in blood pressure in the pithed rat was inhibited by BIBP 3226 dose-dependently (ED50 = 0.11 +/- 0.03 mg/kg i.v.), whereas no effect of BIBP 3226 (1 mg/kg i.v.) was observed for the noradrenaline-, angiotensin-, endothelin- or vasopressin-induced pressor response. The data presented demonstrate that BIBP 3226 is a competitive and NPY Y1-selective antagonist. The peptidic compound proved to possess high potency for NPY Y1 receptors, but showed both agonistic as well as antagonistic properties.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological characterization of the selective nonpeptide neuropeptide Y Y1 receptor antagonist BIBP 3226. 756 41

The expression of vgf gene, first isolated as a gene induced by nerve growth factor in PC12 cells, was investigated in neurons of the suprachiasmatic nucleus (SCN) by in situ hybridization. In the rat forebrain, the vgf mRNA was found most densely in the SCN. Neurons which express vgf mRNA were found both in the dorsomedial and ventrolateral subdivisions. Soluble-labeling of vgf in situ hybridization and peptide immunocytochemistry demonstrated that vgf mRNA was expressed in most vasopressin- and neurophysin-immunoreactive neurons in the dorsomedial part and in vasoactive intestinal peptide (VIP)- and peptide histidine isoleucine amide (PHI)-immunoreactive neurons in the ventrolateral part. These findings suggest that vgf is a highly expressed gene in both vasopressin/neurophysin neurons and VIP/PHI neurons which were speculated to be involved in the generation and entrainment of circadian rhythm.
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PMID:In situ hybridization histochemistry of vgf mRNA in the rat suprachiasmatic nucleus: co-localization with vasopressin/neurophysin and VIP/PHI. 771 6

The expression of vgf gene, first isolated as a gene induced by nerve growth factor in PC12 cells, was investigated in neurons of the suprachiasmatic nucleus (SCN) by in situ hybridization. In the rat forebrain, the vgf mRNA was found most densely in the SCN. Neurons which express vgf mRNA were found both in the dorsomedial and ventrolateral subdivisions. Double-labeling of vgf in situ hybridization and peptide immunocytochemistry demonstrated that vgf mRNA was expressed in most vasopressin- and neurophysin-immunoreactive neurons in the dorsomedial part and in vasoactive intestinal peptide (VIP)- and peptide histidine isoleucine amide (PHI)-immunoreactive neurons in the ventrolateral part. These findings suggest that vgf is a highly expressed gene in both vasopressin/neurophysin neurons and VIP/PHI neurons which were speculated to be involved in the generation and entrainment of circadian rhythm.
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PMID:In situ hybridization histochemistry of vghm1f mRNA in the rat suprachiasmatic nucleus: co-localization with vasopressin/neurophysin and VIP/PHI. 760 15

The relative roles of hypothalamic corticotropin-releasing-hormone (CRH) and vasopressin (AVP) as mediators of the stimulant effect of vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) on ACTH and corticosterone (CORT) secretion, were examined using receptor blockade of endogenous CRH and AVP. ACTH and CORT secretion were stimulated 6- and 7-fold, respectively, by PVN infusion of VIP (3.0 nmol) and 6- and 9-fold, respectively, by PHI (3.0 nmol). ACTH and CORT stimulation by VIP were inhibited 78 and 72%, respectively, by pretreatment with the CRF antagonist, 59 and 57%, respectively, by pretreatment with the AVP antagonist and about 78% by combined pretreatment with the CRF and AVP antagonists. PHI-induced stimulation of ACTH and CORT was inhibited 89 and 81%, 73 and 59% and 93% by pretreatment with the CRF- or AVP-antagonist or combined administration, respectively. These results support the hypothesis that the activation of the hypothalamic-pituitary-adrenal (HPA) axis by VIP and PHI is mediated through the release of endogenous CRH. AVP also plays a role in this response, possibly by enhancing the activity of CRH in a synergistic manner.
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PMID:Involvement of vasopressin and corticotropin-releasing hormone in VIP- and PHI-induced secretion of ACTH and corticosterone. 779 60

Several neuropeptides, including neurotensin, somatostatin, bradykinin, angiotensin II, substance P, and luteinizing hormone-releasing hormone but not vasopressin and oxytocin, were actively metabolized through proteolytic degradation by cultivated astrocytes obtained from rat cerebral cortex. Because phenanthroline was an effective degradation inhibitor, metalloproteases were responsible for neuropeptide fragmentation. Neurotensin was cleaved by astrocytes at the Pro10-Tyr11 and Arg8-Arg9 bonds, whereas somatostatin was cleaved at the Phe6-Phe7 and Thr10-Phe11 bonds. These cleavage sites have been found previously with endopeptidases 24.16 and 24.15 purified from rat brain. Addition of specific inhibitors of these proteases, the dipeptide Pro-Ile and N-[1-(RS)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-4-aminobenzoate, significantly reduced the generation of the above neuropeptide fragments by astrocytes. The presence of endopeptidases 24.16 and 24.15 in homogenates of astrocytes could also be demonstrated by chromatographic separations of supernatant solubilized cell preparations. Proteolytic activity for neurotensin eluted after both gel and hydroxyapatite chromatography at the same positions as found for purified endopeptidase 24.16 or 24.15. In incubation experiments or in chromatographic separations no phosphoramidon-sensitive endopeptidase 24.11 (enkephalinase) or captopril-sensitive peptidyl dipeptidase A (angiotensin-converting enzyme) could be detected in cultivated astrocytes. Because astrocytes embrace the neuronal synapses where neuropeptides are released, we presume that the endopeptidases 24.16 and 24.15 on astrocytes are strategically located to contribute significantly to the inactivation of neurotensin, somatostatin, and other neuropeptides in the brain.
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PMID:Endopeptidases 24.16 and 24.15 are responsible for the degradation of somatostatin, neurotensin, and other neuropeptides by cultivated rat cortical astrocytes. 790 52

The mechanisms for the antidiuretic effects of dynorphin (DYN), an endogenous kappa-agonist, microinjected into the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei were investigated. DYN decreased the urine outflow rate dose-dependently from 5 to 20 nmol in the SON and PVN, and it increased vasopressin release. Microinjection of des-Tyr-DYN (a non-opioid peptide) into the SON produced antidiuretic effects with similar potency to that of the DYN-induced effects. However, in the PVN, the effects of des-Tyr-DYN were very markedly weaker than those of DYN. The DYN-induced antidiureses in the SON were partially inhibited by phenoxybenzamine, timolol and atropine, but not by naloxone. Those in the PVN were partially inhibited by naloxone, timolol and atropine, but not by phenoxybenzamine. Synthetic specific kappa-agonists, U50, 488H and Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro- Arg-Leu-Arg-Gly 5-aminopentylamide (DAKLI), microinjected into the PVN also produced antidiuretic effects in a dose-dependent manner. The order of antidiuretic potency was DAKLI > DYN > U50,488H, which was the same as that of kappa-receptor binding affinity. The DAKLI-induced antidiureses in the PVN were not inhibited by naloxone. These results suggested that DYN caused antidiureses by vasopressin release, through adrenergic and cholinergic mechanisms in the SON and PVN. Only the DYN-induced effects in the PVN were mediated, at least partially, through opioid receptors, perhaps the kappa-subtype.
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PMID:Microinjection of dynorphin into the supraoptic and paraventricular nuclei produces antidiuretic effects through vasopressin release. 790 54

The effects of pituitary adenylate cyclase activating polypeptide (PACAP) on regional blood flow in the eye and other tissues were investigated in albino rabbits. Direct determination of the flow from a cannulated vortex vein, in animals pretreated with a vasopressin receptor antagonist, showed that i.v. infusion of either PACAP-27 or PACAP-38 caused a dose-dependent (0.08-0.64 pmol/kg per min) decrease in the uveal vascular resistance. Regional blood flow was determined, with radioactive microspheres, during i.v. infusion of PACAP-27 or PACAP-38 (0.64 pmol/kg per min) in rabbits pretreated with hexamethonium and a vasopressin receptor antagonist. In these experiments, both PACAP-27 and PACAP-38 increased choroidal blood flow by about 50%, whereas there was no effect in the anterior uvea. Nor was there any major effect on blood flow in the anterior uvea after intracameral injection of PACAP-27 or PACAP-38 (3 pmol). The largest blood flow increases, caused by i.v. infusion of PACAP-27 or PACAP-38, were observed in the parotid gland, submandibular gland, eyelids and nictitating membrane. Local blood flow in the choroid plexus, pineal gland, posterior pituitary gland, stomach, kidney and adrenal gland was also significantly increased during the i.v. infusion of PACAP-27. The results of the present investigation indicate that PACAP-27 and PACAP-38 are about 100 times more potent than vasoactive intestinal polypeptide and peptide histidine isoleucine as vasodilators in the rabbit choroid and, possibly, also in many other tissues of the rabbit.
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PMID:PACAP-27 and PACAP-38: vascular effects in the eye and some other tissues in the rabbit. 791 97

We investigated the involvement of arginine vasopressin (AVP) V1- and V2-receptors in the prolactin (PRL) secretory response to histamine (HA) or restraint stress stimulation in conscious male rats by selective blockade of AVP receptors using different antagonists. Histamine (270 nmol) administered intracerebroventricularly or 5 min of restraint stress stimulated PRL secretion 10-14-fold. Pretreatment with the selective V1-receptor antagonists [1-(p-t-butyl-beta-mercapto-beta, beta-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-D-arginine]vasopressin or [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-arginine]vassopressin inhibited the PRL response to HA and restraint stress in a dose-dependent manner with maximal inhibition of 60%. The effect of the two antagonists was identical when equipotent antivasopressor doses were administered. The selective V2-receptor antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid)-2-D-isoleucine-4-isoleucine-8-arginine]vasopressin was unable to inhibit the PRL response significantly. Combined administration of the V1-receptor antagonist [1-(p-t-butyl-beta-mercapto-beta, beta-cyclopentamethylene propionic acid-2-(O-methyl)tyrosine-8-D-arginine]vasopressin and the V2-receptor antagonist inhibited the PRL response to HA to the same extent as that observed when the V1-antagonist was administered alone. None of the antagonists used had any effect on basal PRL secretion. We conclude that AVP seems to play a role in the mediation of HA- and restraint stress-induced secretion of PRL, and that the AVP receptor involved is primarily of the V1-type or similar to this.
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PMID:Histamine- and stress-induced prolactin secretion: importance of vasopressin V1- and V2-receptors. 792 Dec 29

In contrast to most vertebrate species that possess one oxytocin-like hormone and one vasopressin-like hormone, a few groups, such as marsupials or cartilaginous fishes, are endowed with two peptides of either or both types, suggesting possible gene duplications. We have now isolated two oxytocin-like hormones from the pituitary of the spotted dogfish Scyliorhinus caniculus (suborder Galeoidei). Microsequencing as well as chromatographic and pharmacological comparisons with synthetic peptides show that these peptides are [Asn4,Val8]oxytocin (asvatocin) and [Phe3,Asn4,Val8]-oxytocin (phasvatocin). Asvatocin and phasvatocin display oxytocic activity on rat uterus, about 80 and 5 milliunits per nmol, respectively, and virtually no pressor activity on anesthetized rats. They occur in roughly equal molar amounts in the gland; vasotocin is also present in a proportional amount that is lower by about a factor of 20. In addition to the duality, conservative amino acid substitutions are observed in the two oxytocic peptides in positions 4 (Gln-4-->Asn) and 8 (Leu-8-->Val), when compared with oxytocin. Furthermore, replacement of the isoleucine residue found in position 3 of all other oxytocin-like hormones by phenylalanine in phasvatocin is exceptional; it determines a dramatic decrease of the oxytocic activity. Preservation of the C-terminal-amidated nonapeptide pattern in the 12 vertebrate neurohypophysial hormones known to date suggests that both precursors and processing enzymes have coevolved tightly. On the other hand, whereas the great evolutionary stability of the mature hormones (generally observed in vertebrates) suggests a strict messenger-receptor coevolution, the exceptional diversity found in cartilaginous fishes (six oxytocin-like peptides identified out of eight known) might be due to a looseness of selective constraints, perhaps in relationship with their specific urea osmoregulation.
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PMID:Special evolution of neurohypophysial hormones in cartilaginous fishes: asvatocin and phasvatocin, two oxytocin-like peptides isolated from the spotted dogfish (Scyliorhinus caniculus). 797 45

In this study the interactions of oxytocin with the transmembrane region of the oxytocin receptor were modelled in order to explain the selective binding of oxytocin and vasopressin. Three sites of interaction in the receptors were identified by sequence comparison and model building. Both receptors share one site, which is formed by glutamine residues. This site binds the Asn-5 common to both hormones. The second site is a specific hydrophobic pocket formed by isoleucine and phenylalanine residues. A third interaction is between a conserved tyrosine and the glutamine of vasopressin and oxytocin. The model suggests that one receptor residue in the transmembrane region is responsible for the specificity of the receptors. The model may be used in the rational design of non peptide analogues for the hormones.
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PMID:Modelling the peptide receptor interaction: selectivity of the oxytocin receptor. 806 Mar 40


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