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)

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

The results of the present study describe the course of reaction and the products following chymotrypsin treatment of the oxytocin analogue carbetocin ([1-deamino-1-monocarba-2-O-methyltyrosine]-oxytocin). The metabolites were analyzed and identified through TLC, HPLC and mass spectrometry. The main product emerging after treatment of carbetocin with chymotrypsin is 9-desglycineamide carbetocin indicating preferential hydrolysis of the peptide bond between leucine at position 8 and carboxyterminal glycineamide. At the same time the stability of the bond between tyrosine at position 2 and isoleucine at position 3 appears significantly enhanced through the alkylation of the hydroxyl group of tyrosine.
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PMID:Interaction of chymotrypsin with carbetocin ([1-deamino-1-monocarba-2-O-methyltyrosine]-oxytocin). 933 73

Mammalian pineal gland receives peptidergic (e.g., vasoactive intestinal peptide [VIP]; peptide histidine isoleucine [PHI]; neuropeptide Y, NPY; substance P, calcitonin gene-related peptide [CGRP], arginine vasopressin [AVP] and oxytocin [OXT]) fibers in addition to sympathetic innervation. The dynamics of cAMP efflux and melatonin (MT) secretion were compared during the infusion of these peptides in our long-term perifusion system. VIP and PHI enhanced both pineal cAMP efflux and MT secretion in a dose-dependent manner (10 nM to 10 microM). However, the potency of PHI was slightly less. The peak of cAMP release always precedes that of MT production. The possible interactions between adrenergic and peptidergic compounds in the regulation of pineal cAMP efflux and MT secretion were also studied. VIP acts on specific peptidergic receptors, since its stimulatory effect could only be reduced by a VIP receptor antagonist. VIP has an additive effect at a lower (100 nM) concentration combined with norepinephrine (NE). NPY (100 nM) can completely block NE-induced MT secretion, but the decrease in cAMP efflux is less. However, NPY does not significantly influence VIP-stimulated cAMP efflux or MT secretion. These data suggest that NE, VIP, and NPY are differently involved in the cAMP and calcium signaling. The other neuropeptides are ineffective.
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PMID:Adrenergic and peptidergic control of the regulation of cAMP efflux and melatonin secretion from perifused rat pineal gland. 979 35

The oxytocin (OT)-like peptide of most Australian marsupials is mesotocin (MT), which differs from OT by substitution of isoleucine for leucine at position 8. To date, the only information on the evolution of the OT peptide in marsupials is based on the sequence of the 9-amino acid peptide itself. The main objective of this study was to obtain the nucleotide and derived amino acid sequences of a marsupial MT precursor for comparison with known OT and MT precursors of eutherians and nonmammalian vertebrates. The structural organization and sequence of the MT gene and its specific transcript were established in a macropodid marsupial, the tammar wallaby, using PCR strategies with a combination of genomic DNA and reverse-transcribed hypothalamic RNA. A consensus genomic sequence of 1221 bp was produced which, by comparison with the expressed cDNA sequence, included two intron sequences of 480 and 188 bp. The tammar MT precursor molecule consists of a 32-amino acid signal peptide, followed by the MT-encoding region and the Gly-Lys-Arg carboxy-terminal cleavage and amidation signal which separates the nonapeptide from the 92-amino acid neurophysin. At the amino acid level, the MT precursor is more similar to eutherian OT precursors than to nonmammalian MT, isotocin, or vasotocin precursors. Northern analysis demonstrated a single transcript of approximately 0.6 kB in the hypothalamus. Mesotocin mRNA is also present in several tissues of the reproductive tract, including the corpus luteum, follicle, uterus, and placenta. Within the ovary, MT transcripts are localized predominantly in the granulosa cells of antral follicles with some positive hybridization signals in cells of the theca interna. This pattern of MT gene expression in marsupials is very similar to that of OT in eutherians and suggests a conserved physiology in the mammalian ovary.
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PMID:Mammalian mesotocin: cDNA sequence and expression of an oxytocin-like gene in a macropodid marsupial, the tammar wallaby. 1089 May 61

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

Oxytocin (OXT) is a nine-amino-acid peptide hormone that is mainly released at the times of uterine contractions during parturition and milk ejection during lactation, whereas a similar peptide hormone, arginine vasopressin, primarily exerts direct antidiuretic action on the kidney and causes vasoconstriction of the peripheral vessels. The genes coding for these peptides are tandemly located on the same chromosome. A tandem duplication occurring in the common ancestor of jawed vertebrates has been proposed as responsible. In contrast to the two peptide hormones, only one oxytocin receptor (OXTR) but three arginine vasopressin receptors (AVPR1A, AVPR1B, and AVPR2) are known; these receptors probably arose from two rounds of genome duplication in the common ancestor of vertebrates. In this study, we addressed the molecular evolution of the OXT-OXTR system in eutherians. Our analyses suggest that an amino acid change from isoleucine to lysine on the eighth site (I8L) of the peptide, which corresponded to a change from mesotocin to OXT, had occurred during the common ancestral lineage of eutherians. At around the same time that the emergence of OXT occurred, functional constraints on the OXT receptor (pre-OXTR) might have relaxed, and a series of nonsynonymous substitutions might have accumulated. Only a few of these nonsynonymous substitutions might have contributed to reestablishing the molecular relationship between the OXT ligand and its receptor, after which functional constraints on the OXTR were reinstated. Since the OXT-OXTR system plays an important role in eutherians, the evolution of the OXT-OXTR system was probably an essential component of the genesis of the eutherian signature.
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PMID:Molecular evolution of the oxytocin-oxytocin receptor system in eutherians. 2348 18


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