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 two types of neurophysins known in vertebrate species, namely MSEL-neurophysin (vasopressin-like hormone-associated neurophysin) and VLDV-neurophysin (oxytocin-like hormone-associated neurophysin) have been purified from the pollack (Pollachius virens) pituitary through a combination of molecular sieving and high-pressure liquid chromatography (HPLC). Homogeneity has been checked by gel electrophoresis and return in HPLC. The apparent molecular masses measured by SDS-electrophoresis are near 12 kDa, significantly higher than those found for their mammalian homologues (10 kDa). The two types of neurophysins have been recognized through their N-terminal amino acid sequences. The primary structure of MSEL-neurophysin has been partially determined using automated Edman degradation applied on native and reduced-alkylated protein, as well as peptides derived by trypsin or staphylococcal proteinase hydrolyses. Comparison of pollack MSEL-neurophysin with ox, goose and frog counterparts reveals that particular positions in the polypeptide chain are subjected to substitutions and that the numbers of substitutions do not seem closely related to the paleontological times of divergence between the different vertebrate classes.
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PMID:Bony fish neurophysins. Identification of MSEL- and VLDV-neurophysins of the pollack (Pollachius virens). 798 56

Vasopressin (AVP), the antidiuretic hormone, is a cyclic nonapeptide that acts through binding to G protein-coupled specific membrane receptors pharmacologically divided into three subtypes (V1a, V1b, and V2) linked to distinct second messengers. Within the family of human AVP receptors, the V2 AVP receptor has been cloned, but the structure of the human V1a and V1b AVP receptors remains unknown. We report here the structure and functional expression of a human V1a AVP receptor complementary DNA isolated from human liver cDNA libraries. Cloning and sequencing of a full-length clone isolated a 1472-nucleotide sequence encoding a 418-amino acid polypeptide with seven putative transmembrane domains typical of G protein-coupled receptors. Amino acid sequence identity with the rat liver V1a AVP receptor, the human and rat V2 AVP receptors, and the human oxytocin receptor was 72, 36, 37, and 45%, respectively. Functional characterization of the cloned receptor was done by transient expression in COS-7 cells and stable expression in Chinese hamster ovary cells. Localization of the expressed receptor at the cellular surface was illustrated by using the fluorescent linear analog phenylacetyl-D-Tyr(Et)-Phe-Gln-Asn-Lys-Pro-Arg-NH2 coupled to fluorescein-avidin by dodecabiotin. Competition binding experiments with phenylacetyl-D-Tyr(Et)-Phe-Val-Asn-Lys-Pro-[125I]Tyr-NH2 and AVP analogs revealed high affinity specific binding sites of the V1a subtype. Saturation binding experiments with [3H]AVP confirmed the presence of a single class of high affinity binding sites. Measurement of AVP-induced inositol phosphate production and calcium mobilization confirmed that the expressed V1a AVP receptor is coupled to phospholipase C via a pertussis toxin-insensitive pathway. Thus, the human V1a AVP receptor belongs to the superfamily of seven-transmembrane segment receptors with a significant sequence identity with the other members of the AVP-oxytocin family of receptors.
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PMID:Molecular cloning, sequencing, and functional expression of a cDNA encoding the human V1a vasopressin receptor. 810 69

In addition to the stimulating influence of the sympathetic system on the function of the mammalian pineal gland, neuropeptides such as neuropeptide Y, vasoactive intestinal polypeptide and arginine-vasopressin (AVP) are thought to function as modulators. Since AVP has been shown to influence pineal melatonin synthesis, the aim of the present study was to investigate the possible effects of the second hypothalamic nonapeptide oxytocin (OT), which likewise has been detected in the pineal gland. We therefore studied "synaptic" ribbon (SR) numbers, N-acetyltransferase (NAT) activity and the intracellular concentration of cyclic guanosine monophosphate (cGMP) following in vitro incubation of rat pineals in media containing OT (10(-5) M), noradrenaline (NA, 10(-5) M) or both NA and OT. Pineal glands were derived from rats of three different strains (Sprague-Dawley, Long-Evans and the AVP-deficient strain Brattleboro). Neither morphological nor biochemical analyses showed a difference between control and OT-incubated organs in any of the strains tested. In Brattleboro rats, but not in the other strains, noradrenaline slightly increased the number of SR which was not observed when NA and OT were combined. The addition of NA resulted in distinct augmentation of NAT activity and cGMP content, which were not affected by additional OT application. These results suggest that oxytocin is not crucially involved in the regulation of pineal gland function.
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PMID:Lack of effect of oxytocin on the numbers of "synaptic" ribbons, cyclic guanosine monophosphate and serotonin N-acetyltransferase activity in organ-cultured pineals of three strains of rats. 826 81

Relaxin is a polypeptide hormone best known for its role in parturition. However, high affinity relaxin receptors have been localized in the rat brain and heart in addition to the uterus. Several lines of evidence also suggest that relaxin may be involved in the regulation of blood pressure, heart rate, and the release of oxytocin and vasopressin. We now show by Northern analysis that a 1-kilobase relaxin transcript is detected in the rat brain as well as the ovary of pregnant rats. Using in situ hybridization, relaxin mRNA is localized in discrete regions of the male and female brains, including the anterior olfactory nucleus, tenia tecta, pyriform cortex, neocortex, and hippocampus. Developmental studies show that relaxin mRNA is present in the 1-day postnatal brain, while relaxin receptors are not detectable until 7 days after birth. The relaxin receptor binding affinity was similar in the developing brains, but there was a steady increase in relaxin binding sites during postnatal days 7 to 29, suggesting that relaxin may play a role in brain maturation. While relaxin mRNA is not detected in the heart, high levels of relaxin receptors are detected in the cardiac atrium as early as 1 day after birth. These atrial receptors remained at similar levels throughout postnatal development, suggesting an important role for relaxin in cardiovascular function.
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PMID:Expression of relaxin mRNA and relaxin receptors in postnatal and adult rat brains and hearts. Localization and developmental patterns. 839 68

Mesotocin is the oxytocin-like hormone found in most terrestrial vertebrates from lungfishes to marsupials, which includes all non-mammalian tetrapods (amphibians, reptiles, and birds). It has the largest distribution in vertebrates after vasotocin found in all non-mammalian vertebrates and isotocin identified in bony fishes. In this study, we report the cloning and functional characterization of the cDNA for the mesotocin receptor (MTR) from the urinary bladder of the toad Bufo marinus. The cloned cDNA encodes a polypeptide of 389 amino acids that shows the greatest similarity to the teleost fish isotocin receptor and to mammalian oxytocin receptors with mutations in extracellular loops which are involved in ligand binding. When expressed in COSM6 cells, MTR exhibits the following relative order of ligand affinity: mesotocin > vasotocin = oxytocin > vasopressin > hydrin 1, isotocin, hydrin 2. Injection of MTR cRNA into Xenopus laevis oocytes induces membrane chloride currents in response to mesotocin, which indicates the coupling of the mesotocin receptor to the inositol phosphate/calcium pathway. This response is inhibited by an oxytocin antagonist, but not by a vasopressin antagonist specific for V2 vasopressin receptors. MTR mRNA is not only found in toad urinary bladder, but also in kidney, muscle, and brain tissue of the toad as revealed by northern blot analysis and reverse-transcriptase PCR. The results suggest a variety of function for mesotocin and its receptor including, in particular, an involvement in the regulation of water and salt transport.
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PMID:Cloning and functional characterization of the amphibian mesotocin receptor, a member of the oxytocin/vasopressin receptor superfamily. 864 23

The nucleus tractus solitarii (NTS), which receives visceral afferent information from the cardiovascular, respiratory, gastrointestinal and taste systems, contains multiple neurotransmitters and neuropeptides throughout its rostral to caudal extent. The neurotransmitters and neuropeptides immunoreactivity is located predominately in varicose fibers and small puncta throughout the neuropil. In addition, immunoreactive NTS neurons for a variety of neurotransmitters and neuropeptides are present in subnuclear regions. The neuroactive substances localized immunohistochemically in the NTS include acetylcholine, the neuropeptides, substance P, methionine- and leucine-enkephalin, beta-endorphin, cholecystokinin, neurotensin, galanin, calcitonin gene-related peptide, somatostatin, FMRMamide, neuropeptide Y, angiotensin II, vasoactive intestinal polypeptide, vasopressin, oxytocin, thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, atrial natriuretic peptide, the catecholamines, dopamine, norepinephrine, epinephrine, serotonin, histamine and the amino acids, GABA and glutamate. The pattern of innervation for each neurotransmitter and neuropeptide is not homogeneously distributed throughout the NTS. Each substance has a unique pattern within the NTS as each subnuclear region contains different immunohistochemical staining patterns and densities of fibers. At the ultrastructural level both neurotransmitters and neuropeptides are present in synaptic terminals that are in contact with different parts of the neuronal membranes. Typically, the labeled terminals contain both small, clear vesicles and large, dense core vesicles with the exception of synaptic terminals containing acetylcholine, GABA and glutamate which do not typically have the large, dense core vesicles. The most frequent post-synaptic target are dendrites and spinous processes. Less frequently, synaptic contacts are present on the cell soma.
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PMID:Immunohistochemical localization of neuropeptides and neurotransmitters in the nucleus solitarius. 867 Jul 16

The influence of exogenous signals on circadian rhythms restored by transplants of the suprachiasmatic nucleus (SCN) of the hypothalamus has received little study. The authors tested the responsiveness of hamsters bearing SCN transplants to photic and pharmacological treatments. Light intensities as high as 6,500 lux were insufficient to produce entrainment, although masking was observed frequently. Triazolam failed to produce statistically significant phase shifts when administered during the subjective day, but 2 animals bearing functional SCN grafts responded to this benzodiazapine during the subjective night. The authors next tested the hypothesis that the host can retain circadian aftereffects that influence the period of the circadian system reconstituted by the graft. Intact hamsters were entrained to light:dark cycles of short (23.25-h) and long (25-h) period (T) for at least 3 months. Control hamsters released into constant darkness exhibited profound and long-lasting aftereffects of entrainment to T cycles. Hamsters that received SCN lesions after exposure to these T cycles and SCN grafts 3 weeks later exhibited marginal but statistically significant aftereffects that disappeared within 3 months. On subsequent transfer to constant light, tau lengthened by 0.25 +/- 0.6 h in hamsters with intact SCN (p < .05). Animals bearing SCN grafts continued to free run in constant light but differed from intact animals in that circadian period did not lengthen. Functional SCN grafts contained vasoactive intestinal polypeptide (VIP), neurophysin (NP), and cholecystokinin (CCK) immunoreactive (ir) cells. Inputs of neuropeptide Y-and serotonin-ir fibers from the host brain to grafted SCN peptide cell clusters were variable. Limited observations using retrograde and anterograde tracers do not support the existence of extensive input to the graft. Retinal input overlapped only rarely with clusters of VIP-ir, CCK-ir, or NP-ir cells. The authors conclude that the circadian system reinstated by SCN transplants is relatively impervious to photic influences that exert parametric and nonparametric influences in intact hamsters. The transient expression of aftereffects induced in the host before transplantation indicates that extra-SCN systems of the host can influence the period of the reconstituted circadian system to at least a limited degree.
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PMID:Regulation of the phase and period of circadian rhythms restored by suprachiasmatic transplants. 874 42

Progesterone (P) stimulates prolactin secretion through a neural mechanism in estrogen (E)-primed female monkeys. Several peptides, including beta-endorphin (BE), oxytocin (OT), substance P (SP) and vasoactive intestinal polypeptide (VIP) are potential prolactin stimulatory factors and could mediate the effect of P. We hypothesized that the antagonism of a pivotal peptidergic neural system would block P-induced prolactin secretion and that the function of a pivotal peptidergic system would be altered by changes in gonadal steroid concentrations. Therefore it was of interest (1) to examine the effect of infusion of antagonists to these peptides on P-induced prolactin secretion, and (2) to determine BE, OT, SP and VIP levels in the hypothalamus of monkeys of various reproductive states. For the antagonist studies, female monkeys (n = 8) were spayed, adapted to a vest and tether remote sampling system and catheterized prior to antagonist challenges. E-primed monkeys received P injections 48 h prior to antagonist administration. Prolactin increased within 36-48 h of P injection. All antagonist challenges were administered in varying doses during the P-induced prolactin elevation and blood samples were collected every 10 min for prolactin determinations. The opiate antagonist, naloxone (n = 5), reduced serum prolactin in a dose-related manner with a mean IC50 of 1.5 +/- 0.6 micrograms/kg/min. The OT (n = 4), SP (n = 4) or VIP (n = 4) antagonists did not reduce serum prolactin in a dose-related manner. We previously reported that the hypothalamic content of OT is increased by ovarian hormones. To determine whether the hypothalamic content of BE, SP or VIP was related to gonadal status, the peptide levels in 4 hypothalamic regions of monkeys in various physiological states were measured. BE (ng/mg protein) in the medial basal hypothalamus (MBH) was significantly greater in adult females (17.7 +/- 6.9; n = 6) as compared to spayed females (0.6 +/- 0.2; n = 3) and juvenile females (1.8 +/- 1.1; n = 3). Hypothalamic content of SP in the preoptic area and mammillary bodies, but not the MBH, was significantly greater in gonadal intact females than spayed females. VIP content (pg/mg protein) was not significantly different between adult, spayed and juvenile females nor between adult and juvenile males in any hypothalamic area. Taken together these results support a pivotal role for BE in the neural regulation of P-induced prolactin secretion. The involvement of OT, SP, and VIP in a specific manner at the pituitary level is not indicated.
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PMID:Beta-endorphin, but not oxytocin, substance P or vasoactive-intestinal polypeptide, contributes to progesterone-induced prolactin secretion in monkeys. 879 99

A sheep endometrial oxytocin receptor (OTR) cDNA (1.5 kb) was isolated from a lambda-ZAP library using a reverse transcription-PCR product probe generated from oestrous endometrial mRNA. The sheep OTR cDNA shared an overall similarity of 82% with human OTR cDNA, 85% with pig OTR cDNA and 76% with rat OTR cDNA. The encoded receptor was a 391 amino acid polypeptide 94% similar to human OTR, 94% similar to pig OTR and 93% similar to rat OTR. The sheep OTR contained two additional amino acids compared with human OTR which were located in the highly GC-rich third intracytoplasmic loop. This region is thought to be associated with G protein coupling and signal transduction. Expression of the cDNA in Cos-7 cells and measurement of oxytocin-induced phosphoinositide turnover confirmed that it coded for a functional product. The affinity of the expressed receptor was comparable with that observed for the in vivo receptor.
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PMID:Structure and expression of an ovine endometrial oxytocin receptor cDNA. 880 Jun 44

The mechanisms that regulate mammary blood flow during lactation are not fully understood. In the present study laser Doppler flowmetry (LDF) was used to measure blood flow in the cutaneous microvessels of the mammary gland of lactating rats. The effects of suckling on blood flow were examined, as were those of local injection of oxytocin (0.5-5 mU) and the vasoactive peptides calcitonin gene-related peptide (CGRP; 0.1-10 pmol), vasoactive intestinal polypeptide (VIP; 0.4-20 pmol) and neuropeptide Y (NPY; 1-40 pmol). Blood flow responses to suckling varied depending on how much time had lapsed since the previous suckling. In rats with milk in the gland, suckling caused an initial increase in blood flow. In connection with milk let-down, the blood flow decreased, but was followed by a second increase. In recently suckled rats with no milk in the gland the increase in blood flow corresponded to the number of pups suckling. Oxytocin injections also had varying effects on mammary blood flow depending on how recently suckling had taken place. In non-suckled rats with milk in the gland, oxytocin injections caused a rise in blood flow that was interrupted by a fall during milk ejection. In recently suckled rats, all doses of oxytocin caused an increase in blood flow of similar magnitude. However, the effect of the higher doses had a longer duration. CGRP and VIP injections caused a dose-dependent increase in mammary blood flow regardless of when suckling last occurred. NPY injections caused a dose-dependent decrease in blood flow.
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PMID:Studies on cutaneous blood flow in the mammary gland of lactating rats. 887 41


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