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)

Vasopressin (AVP) and oxytocin (OT) are hypothalamic neuropeptides having distinct peripherally and centrally directed cell populations. While principally responsible for the regulation of osmotic equilibrium, AVP also participates in stress-mediated adrenocorticotropic hormone (ACTH) release, and in consolidation and retrieval of aversively conditioned behaviors. OT is principally known for its role in parturition and lactation, but also has effects opposite of AVP, antagonizing stress-mediated ACTH release and impairing the consolidation and retrieval of aversively conditioned behaviors. Our group has demonstrated novel peripheral osmoregulatory defects in underweight anorexics, coupled with hypersecretion of AVP into the cerebrospinal fluid (CSF). Conversely, a relative reduction of CSF OT is seen in underweight anorexics. Speculatively, these reciprocal changes in neurohypophyseal peptides in the underweight anorexic may enhance the observed neuroendocrine and cognitive abnormalities. In addition, the alterations in CSF OT may occur as a consequence of the abnormal gastrointestinal function present during the acute stages of anorexia nervosa.
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PMID:Neurohypophyseal dysfunction: implications for the pathophysiology of eating disorders. 269 13

The backbone conformations of the cyclic moieties of 1-[beta-mercaptopropionic acid]-oxytocin [( Mpa1]-OT), [1-beta-mercaptopropionic acid]-arginine-vasopressin [( Mpa1]-AVP), [1-(beta'-mercapto-beta,beta-cyclopentamethylene)propionic acid]-arginine-vasopressin [( Cpp1]-AVP), and [1-thiosalicylic acid]-arginine-vasopressin [( Ths1]-AVP) have been analyzed by means of molecular mechanics. In these calculations, the side chains were simulated by pseudoatoms. For the three last compounds, the calculations were also performed on the whole molecules, in order to shed light on the differences in their biological activity. Their starting conformations were obtained by attaching the acyclic tail and side chains to the lowest energy conformations of the cyclic parts. In the case of [Ths1]-AVP, however, other starting conformations were also examined, which were obtained by attaching the planar benzene ring to the lowest energy conformations of [Mpa1]-AVP. In the calculations, all the degrees of freedom were relaxed and Weiner's force field was used, the parameters required for the benzene parts of [Ths1]-AVP being determined from the experimental data available, as well as from the results of molecular dynamics calculations on the model compounds. The lowest energy conformations of [Mpa1]-AVP and [Cpp1]-AVP are similar, while [Ths1]-AVP differs from them near the disulphide region, due to the presence of a planar benzene ring. Interactions involving the charged guanidine group of arginine make, in each case, an important contribution to the conformational energy. A model description of the shapes of the oxytocin and vasopressin ring has been proposed, which is based on the cyclohexane geometry. This description is in good correlation with the energetics of the conformations corresponding to different shapes.
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PMID:Molecular mechanics calculations on deaminooxytocin and on deamino-arginine-vasopressin and its analogues. 271 90

Neurons with intrinsic pacemaker activity and presumed sympathoexcitatory function were recorded in rat tissue slices within the confines of the rostroventrolateral reticular nucleus (RVL). These cells were excited in dose-dependent fashion by arginine vasopressin (AVP, 10(8)-10(6) M) but not by oxytocin (up to 10(7) M). The effect of AVP was mimicked by the V1-selective agonist [Phe2,Orn8]vasotocin (VT) (1 microM) but not by the V2-agonist [Val4,D-Arg8]vasopressin (VP) (1.9 microM). The effect of AVP (10(-7) M) was completely blocked by SKF 101926 (10(7) M), a non-selective antagonist and by d(CH2)5[Tyr(Me)2]AVP, a V1-selective antagonist but was unaffected by the V2-selective antagonist d(CH2)5[D-Ile2,Ile4,Ala-NH2 9]AVP. These cells were also activated by thyrotropin-releasing hormone (TRH) (10(-7)-10(-6) M), calcitonin gene-related peptide (CGRP) (4 X 10(-8) M), substance P, (10(-6) M), neuropeptide Y (NPY) (10(-8) M) and inhibited by Met-enkephalin (10(-6) M) and morphine (2 mM). Corticotropin-releasing factor (CRF) (10(-7) M) and angiotensin II (10(-6) M) were ineffective. In conclusion, RVL pacemaker neurons have vasopressin receptors reminiscent of the V1 (vascular and pressor) subtype. Their pacemaking activity is modulated by low doses of several other peptides also known to produce large vasomotor effects after introduction into the cerebroventricular space.
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PMID:Effects of vasopressin and other neuropeptides on rostral medullary sympathoexcitatory neurons 'in vitro'. 275

Interpretation of studies designed to investigate the inhibitory action of vasopressin on gastric acid secretion has proven difficult, as the in vivo models are potentially susceptible to both direct (e.g. mucosal effects) and indirect effects (e.g. changes in mucosal blood flow). In the present series of experiments we studied vasopressin inhibition of both basal and histamine-stimulated acid secretion in rat isolated gastric mucosa, a preparation which is independent of blood flow. Basal and histamine-stimulated levels of acid secretion were 2.32 +/- 0.10 (mean +/- S.E.) and 4.36 +/- 0.41 mu eqH+/h per cm2. Vasopressin inhibited both basal and histamine-stimulated acid secretion; the effect, which was maximal at 15 min post-dosing, was blocked by the specific V1 antagonist d(CH2)5Tyr(Me) AVP. No effect on acid secretion was evident with either the potent V2 agonist, dDAVP, or oxytocin, a neurohypophyseal hormone which can also affect water retention and blood pressure. These studies demonstrate that vasopressin can specifically inhibit mucosal acid secretion; the inhibitory effect is most likely mediated via a V1 vasopressin receptor subtype on the gastric mucosa.
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PMID:In vitro inhibition of gastric acid secretion by vasopressin. 282 34

Vasopressin and oxytocin immunoreactivity (AVP-IR, OT-IR) have been detected in the trigeminal and dorsal root ganglia (TG, DRG) of the rat. We have investigated whether AVP or OT have any neurotransmitter role in these tissues by measuring the effects of the peptides on levels of intracellular second messengers. AVP and OT at concentrations up to 3 x 10(-6) M have no effect on the accumulation of cAMP. However, in tissue prelabelled with 3H-inositol, and in the presence of 10 mM Li+, AVP and OT cause an increase in the accumulation of inositol phosphates (IP), in a dose-dependent manner. AVP causes a maximum stimulation of 1.7 fold of control in TG, (p less than 0.01) and of 2.5 fold in DRG (p less than 0.01) at a concentration of 3 x 10(-7) M. OT causes a maximum stimulation of 1.3 fold of control in TG, (p less than 0.01), and of 1.75 fold of control in DRG, at a concentration of 3 x 10(-6) M. The stimulation of IP turnover by AVP in both tissues is inhibited by the specific V1-antagonist, (CH2)5Tyr(Me)AVP, at a concentration of 2 x 10(-5) M. The V2-agonist, DDAVP, has no effect on IP accumulation in either tissue at concentrations up to 3 x 10(-6) M. The response to exogenous AVP is still present in ganglia incubated in media without added CaCl2. We conclude that the rat TG and DRG contain receptors for AVP, and that these receptors have characteristics associated with the V1 subtype.
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PMID:Vasopressin-induced turnover of phosphatidylinositol in the sensory nervous system of the rat. 282 10

The stress-induced activation of the corticostimulating function of the pituitary gland was noted to vary according to sex in both the adult and the newborn. The pituitary response in testosterone or estradiol-injected females at the time of birth was similar to that of intact males, in contrast, the castration of the males performed just before the postnatal surge of plasma testosterone was unable to modify at the 8th day, the male characteristic evolution in response to ether inhalation. Present data suggest--in the male, prenatal differentiation of the neuroendocrine pathways involved in the pattern of ACTH release in response to ether inhalation, probably in correlation with the peak of plasma testosterone on day 19 of gestation--in the female, the existence of androgen--sensitive structures in early postnatal life. An alpha stimulatory effect of norepinephrine on these neuroendocrine pathways was suggested. Present report also discuss--the catecholaminergic control of CRF X producing neurons--the sex dependent AVP and/or oxytocin (OT) release induced by a stress--the AVP and OT potentiation of CRF-induced ACTH release.
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PMID:[Perinatal influence of sex hormones on the differential activation of corticotrope function during stress in the male and female]. 282 99

We examined the effect of neurohypophysectomy with and without vasopressin replacement on the ACTH response to hypotension and ovine CRF infusion and on the adrenocortical response to ACTH and angiotensin II infusion in conscious dogs. Nitroprusside hypotension (decrease in mean arterial pressure of 25 mm Hg) in the intact state resulted in large increases in plasma arginine vasopressin (pAVP; from 2.6 +/- 0.3 to 296 +/- 63 pg/ml) and ACTH (from 35 +/- 6 to 395 +/- 92 pg/ml). Neurohypophysectomy resulted in greatly attenuated pAVP (8.4 +/- 1.6 pg/ml) and ACTH (80 +/- 10 pg/ml) responses to hypotension which were not normalized by physiological low dose vasopressin replacement (6-18 pg/kg.min continuously, iv, for 2 weeks). However, acute administration of vasopressin (4-6 ng/kg.min) simultaneously with hypotension in the neurohypophysectomized (neurohypox) dog, which produced pAVP levels equivalent to the hypotensive response to intact dogs, almost completely normalized the ACTH response to hypotension (to 248 +/- 74 pg/ml). The ACTH response to 20 ng/kg.min ovine CRF, iv (from 43 +/- 8 to 268 +/- 77 pg/ml), was not attenuated by neurohypophysectomy. The cortisol responses to infusion of 0.5 and 2 ng/kg.min ACTH-(1-24), iv, were essentially normal in neurohypox dogs. However, the ACTH and aldosterone responses to 5 ng/kg.min angiotensin II infusion iv were attenuated in neurohypox dogs off AVP replacement. Histological examination revealed normal adrenal glands and anterior pituitaries in neurohypox dogs. Immunocytochemical staining for vasopressin and neurophysin revealed normal cell bodies in the paraventricular and supraoptic nuclei of the hypothalami from neurohypox dogs. However, median eminence staining for AVP and neurophysin was greatly diminished in neurohypox dogs. In summary, neurohypophysectomy 1) attenuated the ACTH response to hypotension and angiotensin II, but not to CRF, and 2) attenuated the aldosterone response to high dose angiotensin II. Furthermore, the deficit in ACTH secretion was almost completely normalized by increasing plasma AVP levels to those observed in the intact dogs. We conclude that an action of circulating pAVP increases ACTH secretion by a direct effect at the pituitary and by activating afferent input to the hypothalamus.
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PMID:Control of adrenocorticotropin secretion and adrenocortical sensitivity in neurohypophysectomized conscious dogs: effects of acute and chronic vasopressin replacement. 283 Oct 29

Sites which bind tritiated vasopressin (AVP) with high affinity were detected in the brain of male, adult rats, by light microscopic autoradiography. Their anatomical localization differed markedly from that of high affinity binding sites for tritiated oxytocin (OT) determined in the same animal. Co-labelling was minimized by using low concentrations of [3H]AVP and [3H]OT. Binding of the former occurred predominantly in several structures of the limbic system (septum, amygdala, bed nucleus of the stria terminalis, accumbens nucleus), in two hypothalamic nuclei (suprachiasmatic and dorsal tuber) and in the area of the nucleus of the solitary tract. Binding of OT was evidenced in the olfactory tubercle, the ventromedial hypothalamic nucleus, the central amygdaloid nucleus and the ventral hippocampus. The ligand specificity of the binding sites was assessed in competition experiments. Synthetic structural analogues were used, allowing to discriminate OT receptors (OH[Thr4,Gly7]OT) from V2 receptors (dDAVP and d[Tyr(Me)2]VDAVP), V1 receptors ([Phe2,Orn8]VT) and V1b receptors (desGly9d(CH2)5AVP). Our main conclusions are, firstly, that AVP and OT binding sites can be readily distinguished, and that there is virtually no overlap in their distribution in the rat brain. Second, we showed that the sites which bind AVP with high affinity in the brain are V1 receptors, different both from the renal V2 receptors and from the anterior pituitary V1b receptors. Our results support the conjecture that AVP and OT play a role in interneuronal communication in the brain.
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PMID:Localization and pharmacological characterization of high affinity binding sites for vasopressin and oxytocin in the rat brain by light microscopic autoradiography. 283 8

In view of the presence of distinct oxytocin (OT) and vasopressin (VP) receptors in the male genital tract (porcine) we have reexamined the receptors for OT and AVP in the classical OT target tissue, female genital tract (rabbit). Neurohypophysial hormone receptors have been investigated in vagina, myometrium, and oviduct using quantitative ligand binding, adenylate cyclase, and contractility studies. Our results clearly indicate the presence of distinct OT and V1 VP receptors in the myometrium, while only the latter was detected in vagina and oviduct. In myometrium, estrogen treatment increases the density of OT and AVP receptors, while progesterone administration inhibits the estrogen effect. At the time of spontaneous delivery a dramatic (17-fold) increase was observed for the OT sites, while the AVP sites were unchanged. AVP receptors in vagina were sensitive to sex steroid administration and were reduced during pregnancy and delivery. Isometric contractility studies suggest that not just OT, but AVP can stimulate uterine strips, an effect that is partially reversible by the V1 antagonist d(CH2)5TyrMeAVP. In vagina only AVP is effective in inducing contractions at nanomolar concentrations. These results suggest a role for AVP as well as OT in regulation of the motility of female genital tract.
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PMID:Vasopressin and oxytocin receptors in vagina, myometrium, and oviduct of rabbits. 283 78

We have investigated the importance of endogenous opioids in the differential control of neurohypophysial peptide secretion. The effect of the opioid antagonist naloxone on the vasopressin and oxytocin responses to insulin-induced hypoglycemia was studied in 14 male subjects. Either saline (N = 8) or naloxone (4 mg bolus + 6 mg/h, N = 6) was infused iv during the study. After 60 min infusion soluble insulin 0.15 U/kg was injected. Naloxone infusion for 60 min did not alter basal plasma AVP or OT levels. Insulin-induced hypoglycemia led to a significant rise in plasma AVP in both saline and naloxone-infused subjects (P less than 0.05), which was maximal 45 min after insulin. There was no significant difference in the plasma AVP response to hypoglycemia between the 2 groups. Saline-infused subjects did not show any change in plasma OT in response to hypoglycemia whilst during concurrent naloxone infusion there was a significant rise in OT from 1.9 +/- 0.4 pmol/l before insulin to 3.2 +/- 1.3 pmol/l at 45 min (P less than 0.05). We conclude that there is opioid-mediated inhibition of OT which prevents its release when AVP is secreted in response to insulin-induced hypoglycemia.
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PMID:Opioid-mediated inhibition of oxytocin during insulin-induced hypoglycemic stimulation of vasopressin in man. 283 96


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