Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects on social recognition memory of (Arg(8))-vasopressin (AVP-(1-9), [pGlu(4), Cyt(6)]AVP-(4-8) and oxytocin locally administered into the rat's septum were investigated. In the behavioural paradigm used, a juvenile intruder was presented to an adult resident male rat twice for 5 min, with an inter-exposure interval of 120 min. Peptide-free residents investigated the juvenile during the second encounter as long as during the first encounter. Intraseptal injection just after the first encounter with graded doses of (Arg(8))-vasopressin, [pGlu(4),Cyt(6)]AVP-(4-8) or oxytocin caused a decrease of social investigation, as compared to placebo treatment, indicating facilitation of social recognition. The least effective dose was 100pg, 200pg and 300pg respectively. The action of vasopressin was blocked by both d(CH(2))(5)[Tyr(Me)(2)]AVP and d(CH(2))(5)[D-Ile(2)Ile(4)]AVP, V(1) and V(2) vasopressinergic receptor antagonists, but not by desGly(NH(2))(9)-d(CH(2))(5)[Tyr(Me)(2)Thr(4)]-OVT, an oxytocinergic receptor antagonist. None of the antagonists blocked the oxytocin-facilitating action on social recognition. They also did not affect social recognition when injected alone. The effects of vasopressin seem to be mediated by vasopressinergic receptors dissimilar to those found in the periphery, while the receptors involved in the action of oxytocin remain to be elucidated.
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PMID:Neurohypophyseal hormone receptors in the septum are implicated in social recognition in the rat. 1122 37

Using a segment strategy, we have synthesized four iodinated photoactivatable cyclic peptidic ligands of oxytocin, bearing a beta-mercapto-betabeta-cyclopentamethylene propionic group (Pmp) on their N-terminus. All the syntheses were RP-HPLC monitored, and the compounds were HPLC purified. They were characterized by 1H NMR, MALDI-TOF, or FAB mass spectrometries. The affinities of Pmp-Tyr(Me)-Ile-Thr-Asn-Cys-Gly-Orn-Phe(3I,4N3)-NH2 (20), Pmp-Tyr-Ile-Thr-Asn-Cys-Gly-Orn-Phe(3I,4N3)-NH2 (21), Pmp-Tyr(Me)-Ile-Thr-Asn-Cys-Pro-Orn-Phe(3I,4N3)-NH2 (22), and Pmp-Tyr-Ile-Thr-Asn-Cys-Pro-Orn-Phe(3I,4N3)-NH2 (23) were evaluated as inhibition constants (K(i), in nM) for the human oxytocin receptor expressed in Chinese hamster ovary cells by displacement of a radioiodinated disulfide-cyclized antagonist (Elands et al. Eur. J. Pharmacol. 1987, 147, 197-207). The most potent of them, compound 22, was synthesized by another method in order to allow its radiolabeling by 125I. Its dissociation constant (K(d)) for the human oxytocin receptor, directly measured in saturation studies, was 0.25 +/- 0.04 nM, and its antagonist properties were determined by inactivation of phospholipase C, thus obtaining an inactivation constant (K(inact)) of 0.18 +/- 0.02 nM, evaluated by inositol phosphate accumulation. This compound is a very good tool for the mapping of peptidic antagonist binding sites in the human oxytocin receptor.
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PMID:Design, synthesis and pharmacological characterization of a potent radioiodinated and photoactivatable peptidic oxytocin antagonist. 1152 Feb 11

Neurohypophysial hormones have been so far identified in Neopterygii and Crossopterygii but not in species of the bird sub-class of bony fishes, the Palaeopterygii. Isolation and chemical characterization of the active principles of a primitive bony fish, Polypterus bichir, have been performed. Isotocin (Ser(4)-Ile(8)-oxytocin) and arginine vasotocin (Arg(8)-oxytocin) have been identified. Because the same peptides were found in the recent Neopterygii, it can be deduced that neurohypophysial hormones have displayed a peculiar stability in the course of the evolution of bony fishes. However isotocin and vasotocin are replaced by oxytocin and vasopressins in mammals and therefore might be regarded as "old" molecules.
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PMID:Molecular evolution of the neurohypophysial hormones: The active peptides of a primitive bony fish Polypterus bichir. 1194 19

Oxytocin is a neurohypophyseal peptide hormone that induces labor and lactation in mammals. An inverse gamma-turn mimetic corresponding to the tripeptide Ile-Val-Asn has been synthesized and incorporated instead of residues 3-5 of oxytocin to probe the hypothesis that a gamma-turn involving these residues is found in the receptor bound conformation of oxytocin. In the turn mimetic, residues i and i + 1 are connected by a psi[CH(2)O] isostere while a covalent methylene bridge replaces the hydrogen bond that is often found between residues i and i + 2 in gamma-turns. The turn mimetic was assembled from three types of building blocks: an azido epoxide, an alpha-bromo acid, and a protected beta-amino alcohol. The oxytocin analogue did not induce contractions of the uterus nor did it inhibit oxytocin-induced contractions. It is suggested that the loss of bioactivity is mainly due to the presence of a psi[CH(2)O] isostere instead of an amide bond between residues i and i + 1 in the turn mimetic.
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PMID:Synthesis and pharmacological evaluation of an analogue of the peptide hormone oxytocin that contains a mimetic of an inverse gamma-turn. 1203 59

The parenchymal cells of the mammalian pineal gland are the hormone-producing pinealocytes and the interstitial cells. In addition, perivascular phagocytes are present. The phagocytes share antigenic properties with microglial and antigen-presenting cells. In certain species, the pineal gland also contains neurons and/or neuron-like peptidergic cells. The peptidergic cells might influence the pinealocyte by a paracrine secretion of the peptide. Nerve fibers innervating the mammalian pineal gland originate from perikarya located in the sympathetic superior cervical ganglion and the parasympathetic sphenopalatine and otic ganglia. The sympathetic nerve fibers contain norepinephrine and neuropeptide Y as neurotransmitters. The parasympathetic nerve fibers contain vasoactive intestinal peptide and peptide histidine isoleucine. Recently, neurons in the trigeminal ganglion, containing substance P, calcitonin gene-related peptide, and pituitary adenylate cyclase-activating peptide, have been shown to project to the mammalian pineal gland. Finally, nerve fibers originating from perikarya located in the brain containing, for example, GABA, orexin, serotonin, histamine, oxytocin, and vasopressin innervate the pineal gland directly via the pineal stalk. Biochemical studies have demonstrated numerous receptors on the pinealocyte cell membrane, which are able to bind the neurotransmitters located in the pinealopetal nerve fibers. These findings indicate that the mammalian pinealocyte can be influenced by a plethora of neurotransmitters.
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PMID:The anatomy and innervation of the mammalian pineal gland. 1211 44

Peptide histidine isoleucine (PHI) and VIP are derived from the same precursor. While central VIP decreases food intake, potential effects of PHI on feeding have not been studied. In the current study, we found that PHI administered intracerebroventricularly (ICV) or into the hypothalamic paraventricular nucleus (PVN) or central nucleus of the amygdala (CeA) decreased food consumption in overnight-deprived rats. The magnitude of an anorexigenic response to PHI differed depending on the injection route: ICV-infused peptide evoked the most potent effect. We determined that that only PVN- and CeA-injected PHI did not have aversive consequences. In addition, we infused anorexigenic doses of PHI via the same routes and assessed Fos immunoreactivity of PVN oxytocin (OT) and vasopressin (VP) neurons using double immunohistochemistry. OT and VP are thought to promote feeding termination. PHI increased the percentage of Fos-positive OT neurons regardless of the injection route. PVN- and ICV-infused PHI induced activation of VP cells. We conclude that central PHI has an inhibitory influence on food intake in rats. The PVN, with OT and VP neurons, and CeA may be involved in the mediation of anorexigenic effects of PHI.
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PMID:Peptides that regulate food intake: effect of peptide histidine isoleucine on consummatory behavior in rats. 1259 79

A mouse bearing a novel transgene encoding the human VPAC2 receptor (hVIPR; Shen et al. (2000) PNAS, 97, 11575-11580) was used to investigate circadian function in the hypothalamic suprachiasmatic nuclei (SCN). Neurons expressing hVPAC2R, detected by a beta-galactosidase (beta-GAL) tag, have a distinct distribution within the SCN, closely matching that of neurophysin (NP) neurons and extending into the region of peptide histidine isoleucine (PHI) cells. In common with NP and PHI cells, neurons expressing hVPAC2R are circadian in nature, as revealed by synchronous rhythmic expression of mPERIOD (mPER) proteins. A population of SCN cells not expressing PHI, NP or hVPAC2R exhibited circadian PER expression antiphasic with the rest of the SCN. Nocturnal light exposure induced mPER1 in the ventral SCN and mPER2 widely across the nucleus. Induction of nuclear mPER2 in hVPAC2R cells confirmed their photic responsiveness. Having established their circadian properties, we tested the utility of SCN neurons expressing the hVIPR transgene as functionally and anatomically explicit markers for SCN tissue grafts. Prenatal SCN tissue from hVIPR transgenic pups survived transplantation into adult CD1 mice, and expressed beta-GAL, PER and PHI. Over a series of studies, hVIPR transgenic SCN grafts restored circadian activity rhythms to 17 of 72 arrhythmic SCN lesioned recipients (23.6%). By using heterozygous hVIPR transgenic grafts on a heterozygous Clock mutant background we confirmed that restored activity rhythms were conferred by the donor tissue. We conclude that the hVIPR transgene is a powerful and flexible tool for examination of circadian function in the mouse SCN.
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PMID:A hVIPR transgene as a novel tool for the analysis of circadian function in the mouse suprachiasmatic nucleus. 1281 56

A mouse bearing a novel transgene encoding the human VPAC2 receptor (hVIPR; Shen et al. (2000) PNAS, 97, 11575-11580) was used to investigate circadian function in the hypothalamic suprachiasmatic nuclei (SCN). Neurons expressing hVPAC2R, detected by a beta-galactosidase (beta-GAL) tag, have a distinct distribution within the SCN, closely matching that of neurophysin (NP) neurons and extending into the region of peptide histidine isoleucine (PHI) cells. In common with NP and PHI cells, neurons expressing hVPAC2R are circadian in nature, as revealed by synchronous rhythmic expression of mPERIOD (mPER) proteins. A population of SCN cells not expressing PHI, NP or hVPAC2R exhibited circadian PER expression antiphasic with the rest of the SCN. Nocturnal light exposure induced mPER1 in the ventral SCN and mPER2 widely across the nucleus. Induction of nuclear mPER2 in hVPAC2R cells confirmed their photic responsiveness. Having established their circadian properties, we tested the utility of SCN neurons expressing the hVIPR transgene as functionally and anatomically explicit markers for SCN tissue grafts. Prenatal SCN tissue from hVIPR transgenic pups survived transplantation into adult CD1 mice, and expressed beta-GAL, PER and PHI. Over a series of studies, hVIPR transgenic SCN grafts restored circadian activity rhythms to 17 of 72 arrhythmic SCN lesioned recipients (23.6%). By using heterozygous hVIPR transgenic grafts on a heterozygous Clock mutant background we confirmed that restored activity rhythms were conferred by the donor tissue. We conclude that the hVIPR transgene is a powerful and flexible tool for examination of circadian function in the mouse SCN.
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PMID:A hVIPR transgene as a novel tool for the analysis of circadian function in the mouse suprachiasmatic nucleus. 1260 72

Quantitative assays of four synthetic peptides related to oxytocin were carried out on the post partum human uterus in vivo by means of external tocography. The following activities (U/mg, means and standard errors) were found: isoleucine(8)-oxytocin 365+/-70, asparagine(4)-oxytocin 150+/-40, desamino(1)-oxytocin 1,030+/-300, serine(4)-isoleucine(8)-oxytocin 335+/-95. None of the conventional bioassay procedures proved to be fully reliable for predicting the oxytocic activity in man of peptides related to oxytocin. If the tocographically recorded effects of equipotent doses of the compounds are compared with those of oxytocin no qualitative differences can be observed.
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PMID:QUANTITATIVE COMPARISON BETWEEN OXYTOCIN AND FOUR RELATED NEUROHYPOPSIAL PEPTIDES ON THE HUMAN UTERUS IN SITU. 1420 93

The glutamine(4) residue in [deamino-Cys(1)]arginine vasopressin (dAVP) was replaced by a broad series of aliphatic, aromatic, polar, and charged amino acids to give the following peptides: d[Gly(4)]AVP (1), d[Ala(4)]AVP (2), d[Abu(4)]AVP (3), d[Nva(4)]AVP (4), d[Nle(4)]AVP (5), d[Leu(4)]AVP (6), d[Ile(4)]AVP (7), d[Thi(4)]AVP (8), d[Phe(4)]AVP (9), d[Tyr(4)]AVP (10), d[Trp(4)]AVP (11), d[Asn(4)]AVP (12), d[Ser(4)]AVP (13), d[Thr(4)]AVP (14), d[Dap(4)]AVP (15), d[Dab(4)]AVP (16), d[Orn(4)]AVP (17), d[Lys(4)]AVP (18), d[Arg(4)]AVP (19), d[Har(4)]AVP (20), and d[Glu(4)]AVP (21). All peptides were synthesized by solid-phase methods using BOC chemistry for all but one peptide (8), which required the use of Fmoc chemistry. The binding and functional properties of these position 4 substituted analogues of dAVP (d[X(4)]AVP) and the previously reported d[Cha(4)]AVP (Derick et al. Endocrinology 2002, 143, 4655-4664) were evaluated on human arginine vasopressin (AVP) V(1a), V(1b), and V(2) receptors and on the human oxytocin (OT) receptor expressed in living Chinese hamster ovary (CHO) cells. Binding studies revealed that broad modifications of the fourth residue of dAVP do not significantly alter affinity for the human V(1b) receptor. Only aromatic (Phe, Tyr, Trp) or negatively charged (Glu) residues reduce V(1b) affinity. By contrast, the human V(1a) and more particularly the human V(2) and the OT receptors are more sensitive to many of these modifications. Thus, the replacement of the Gln(4) residue of dAVP by aliphatic (Leu, Cha) or positively charged (Orn, Lys, Arg, Har) amino acids led to analogues exhibiting drastic reductions of their affinity for the human V(1a), V(2), and OT receptors. Consequently, in addition to the previously reported d[Cha(4)]AVP, peptides 6 and 17-20 display excellent selectivities for the human V(1b) receptor. The key structural requirement responsible for optimal V(1b) selectivity appears to be the length and branching of the aliphatic side chain of the fourth residue of dAVP. Functional studies performed on CHO cells expressing the different human AVP/OT receptors confirm the V(1b) selectivity of peptides 6, 17, 18, 20, and d[Cha(4)]AVP. However, d[Arg(4)]AVP (19), which triggers an excellent coupling between the human V(2) receptor and adenylyl cyclase, was found to exhibit both V(1b) and V(2) agonism in functional tests. More interestingly, these functional experiments revealed that, depending on the AVP/OT receptor, a given d[X(4)]AVP analogue may behave as a full agonist or as a partial agonist. This strongly suggests that the fourth residue of dAVP plays an important role in the coupling between the hormone-receptor complex, the heterotrimeric G protein, and the effectors. In conclusion, the synthesis of these d[X(4)]AVP analogues led to the discovery of new V(1b) agonists with high affinity and greatly enhanced selectivities. Thus, in addition to d[Cha(4)]AVP, d[Leu(4)]AVP (6), d[Orn(4)]AVP (17), d[Lys(4)]AVP (18), and d[Har(4)]AVP (20) are useful new tools for studying the structure and the function of the human V(1b) receptor.
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PMID:Design of potent and selective agonists for the human vasopressin V1b receptor based on modifications of [deamino-cys1]arginine vasopressin at position 4. 1508 36


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