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)

Nerve endings of the magnocellular neurohypophysial neurones possess kappa-opioid receptors. Using a preparation of isolated terminals from the neurohypophysis we studied kappa-opioid effects on secretion of oxytocin and vasopressin and on intracellular Ca2+ concentration ([Ca2+]i) measured fluorimetrically or using digital video imaging with Fura-2. The dihydropyridine Ca(2+)-channel antagonist nicardipine reduced [Ca2+]i responses to K(+)-depolarisation (30-40 mM K+) by 55-75% and inhibited evoked secretion of oxytocin and vasopressin to a similar extent. The selective kappa-receptor agonist D-Pro10 Dynorphin A 1-11 (DPDYN) substantially inhibited K+ evoked secretion of oxytocin by 40-90% and secretion of arginine vasopressin (AVP) by 20-50%. DPDYN caused only a 10% reduction in the average total population [Ca2+]i response to K+ depolarisation. No sub-population of inhibitory responses was observed when samples of individual terminal [Ca2+]i responses were examined with imaging. Although kappa-receptors are coupled to Ca(2+)-channels at neuronal somata our data suggest that alternative effector mechanisms operate in these secretory nerve endings.
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PMID:Activation of kappa-opioid receptors inhibits depolarisation-evoked exocytosis but not the rise in intracellular Ca2+ in secretory nerve terminals of the neurohypophysis. 135 98

Rat neural lobes and isolated nerve terminals from the neurohypophysis were stimulated in the presence of different opioid agonists and antagonists. The secretion of arginine vasopressin and oxytocin and rise in cytoplasmic calcium induced by depolarization were analyzed by radioimmunoassay and the fluorescent probe fura-2, respectively. The kappa-agonists dynorphin A(1-13) and dynorphin A(1-8) did not affect electrically evoked release of vasopressin, although oxytocin release was slightly reduced. U-50 488, a relatively specific kappa-receptor agonist, had no effect on the amount of vasopressin or oxytocin secreted, although it significantly reduced K(+)-evoked changes in [Ca2+]i in isolated nerve endings. Two kappa-receptor antagonists, MR 2266 and diprenorphin, alone had no effect on vasopressin and oxytocin secretion from isolated nerve endings depolarized with potassium. Opioid agonists less selective for the kappa receptors, etorphin and ethylketocyclazocin, were found to inhibit the release of both vasopressin and oxytocin significantly. Naloxone, a nonselective opiate receptor antagonist, alone had no effect on vasopressin release but potentiated the electrically evoked release of oxytocin. Naloxone also could overcome the inhibitory effect of etorphin on oxytocin and vasopressin release observed after electrical stimulation of the neural lobe. A number of inconsistencies therefore exist between the effects of opioid agonists and antagonists on neuropeptide release and on the evoked changes in [Ca2+]i. In view of these inconsistencies and the high concentrations of opioid agonists and antagonists necessary to modify release, we conclude that it is doubtful that opioid molecules have a physiological role in controlling neurohypophysial secretion.
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PMID:Intracellular calcium and hormone release from nerve endings of the neurohypophysis in the presence of opioid agonists and antagonists. 135 68

The effects of beta-endorphin, Met-enkephalin, dynorphin and SKF 10047 on the constancy of the isometric developed tension (IDT) of the spontaneous contractions of uterine strips isolated from ovariectomized rats were explored. beta-endorphin (10(-6) M) was the only opioid that depressed significantly uterine constancy of IDT in a concentration dependent fashion. Naloxone, neither at 10(-8) M nor at 10(-6) M, altered the negative inotropic influence of beta-endorphin. Moreover, the basal synthesis and outputs of some prostaglandins (PGE1, PGE2 and PGF2 alpha) from rat uteri and the effect of beta-endorphin (10(-6) M), were determined. It was found that the basal synthesis and release of PGs in uteri were significantly inhibited by this endogenous opioid. The effects of beta-endorphin (10(-8), 10(-6) and 10(-5) M) on the basal; and oxytocin or A23187, induced 45Ca2+ uptake, as well as the influence of naloxone were also studied. beta-endorphin at three of the concentrations tested decreased basal uterine 45Ca2+ uptake and this action was not prevented by naloxone (10(-8) M). The presence of oxytocin and of A23187 augmented significantly 45Ca2+ uptake, an effect that was antagonized by beta-endorphin (10(-6) M). The possible role of beta-endorphin in uterine functioning via the modulation of uterine PG synthesis and Ca2+ uptake is discussed.
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PMID:Effects of beta-endorphin on spontaneous uterine contractions. Prostaglandins production and 45Ca2+ uptake in uterine strips from ovariectomized rats. 135 70

Cerebrospinal fluid hormones, monoaminergic metabolites, and dynorphin A (1-8 sequence) were examined in 43 children with severe, primary obsessive-compulsive disorder. Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid were positively correlated with one of eight obsessive-compulsive disorder severity ratings and three of seven measures of improvement following 5 weeks of treatment with clomipramine hydrochloride. Arginine vasopressin concentration was significantly and negatively correlated with several ratings of obsessive-compulsive disorder symptom severity, while oxytocin concentration was positively correlated with depressive symptoms. The ratio of arginine vasopressin to oxytocin was also negatively correlated with obsessive-compulsive disorder and depressive symptoms. Comorbid affective disorder was associated with decreased arginine vasopressin concentrations, while concomitant anxiety disorder was associated with increased oxytocin. Dynorphin A (1-8 sequence), homovanillic acid, corticotropin, 3-methoxy-4-hydroxyphenylglycol, and corticotropin releasing hormone were not significantly related to obsessive-compulsive disorder symptoms. These results seem to indicate that arginine vasopressin may be related to obsessive-compulsive disorder symptom severity, while 5-hydroxyindoleacetic acid might be associated with drug response.
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PMID:Cerebrospinal fluid neurochemistry in children and adolescents with obsessive-compulsive disorder. 137 Jan 97

The hypothalamo-neurohypophyseal tract is known to contain the classical neurohypophyseal hormones vasopressin and oxytocin. Additionally, dynorphin, methionine- and leucine-enkephalin, cholecystokinin (CCK), corticotropin-releasing factor (CRF), and galanin are co-stored with vasopressin and/or oxytocin. Recent immunohistochemical studies have revealed the existence of a low to moderate number of substance P-, vasoactive intestinal peptide (VIP)-, neuropeptide Y (NPY)- and somatostatin-immunoreactive nerve fibers within the rat neurohypophysis. VIP-, substance P- and NPY-immunoreactive fibers were distributed throughout the organ, whereas somatostatin-immunoreactive fibers were present in the proximal part of the organ. The positive nerve endings were either large in size resembling classical nerve terminals related to perivascular spaces, or smaller similar to peptidergic fibers as described in the CNS. These results indicate that these neuropeptides may be either co-stored with the classical neurohypophyseal hormones or contained in another system of afferents to the organ. The probably distinct functional roles of these neuropeptides in the physiology of the neurohypophysis are discussed.
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PMID:Non-vasopressinergic, non-oxytocinergic neuropeptides in the rat hypothalamo-neurohypophyseal tract: experimental immunohistochemical studies. 138 83

The topographical distribution of neuropeptide-containing cell bodies, fibers and terminals was studied in human parabrachial nuclei and the pontine tegmentum with immunohistochemical stainings. Brains of seven adult human subjects of 35-72 years were fixed within 2 h post mortem. Serial sections were immunostained by antisera of 14 different neuropeptides--oxytocin, vasopressin, thyrotropin-releasing hormone, angiotensin II, calcitonin gene-related peptide, beta-endorphin, dynorphin A, dynorphin B, leucine-enkephalin, alpha-melanocyte stimulating hormone, substance P, neuropeptide Y, cholecystokinin and galanin--alternately. All of these peptides were found to be present in nerve fibers and terminals, but only two, angiotensin II and dynorphin B, in cell bodies of the parabrachial nuclei. Calcitonin gene-related peptide-, neuropeptide Y-, cholecystokinin- and galanin-immunoreactive cells were present in other areas of the pontine tegmentum, like the motor trigeminal nucleus, locus coeruleus, periventricular gray matter but not in the parabrachial nuclei. Peptidergic fibers were distributed unevenly throughout the pontine tegmentum having unique, individual distribution patterns. In the parabrachial nuclei, substance P, neuropeptide Y, cholecystokinin and galanin showed the highest density of immunoreactive neuronal networks. Moderate to low concentrations of immunoreactive processes were detected by calcitonin gene-related peptide, alpha-melanocyte stimulating hormone, dynorphin B, thyrotropin releasing hormone, leucine-enkephalin, dynorphin A, angiotensin II, beta-endorphin, vasopressin and oxytocin antisera, respectively. Other pontine tegmental areas, like the locus coeruleus, dorsal tegmental, pontine raphe and motor trigeminal nuclei as well as the central gray of the tegmental region exhibited a varying assortment of neuropeptides with distinct, individual localization patterns. Their detailed topographical distributions are mapped and given in coronal sections.
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PMID:Immunohistochemical study on the distribution of neuropeptides within the pontine tegmentum--particularly the parabrachial nuclei and the locus coeruleus of the human brain. 154 21

Studies performed in conscious female rats confirmed that iv injection of cholecystokinin octapeptide (CCK; 20 mu/kg) increased the circulating concentration of oxytocin but not that of vasopressin, and confirmed that the stimulation of oxytocin release was markedly facilitated after iv administration of naloxone (1 mg/kg), indicating attenuation of oxytocin release by endogenous opioids. To investigate the site of action of the endogenous opioids, the electrical activity of putative oxytocin neurones in the supraoptic nucleus was recorded in urethane-anaesthetised female rats. Oxytocin neurones responded to CCK injection with an increase in firing rate lasting 5-15 min, but this response was not facilitated by prior injection of naloxone. The results suggest that the opioid influence upon CCK-induced oxytocin release operates at the level of the neurosecretory terminals in the neurohypophysis rather than centrally. Since CCK does not elevate vasopressin release, it appears unlikely that dynorphin, the opioid peptide co-existing with vasopressin, is responsible in these circumstances for the cross-inhibition of oxytocin release. It is suggested that products of proenkephalin A, the met-enkephalin precursor present in the supraoptic nucleus and in the neurohypophysis itself, may be active in the regulation of oxytocin release.
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PMID:Naloxone potentiates the release of oxytocin induced by systemic administration of cholecystokinin without enhancing the electrical activity of supraoptic oxytocin neurones. 157 6

Naloxone and its congener, methyl naloxone, were given subcutaneously (s.c.) or centrally (i.c.v.) to 24-h water-deprived male rats 30 min prior to decapitation and the effect on plasma levels of vasopressin (VP) and oxytocin (OT) was studied. The potency of s.c. applied methyl naloxone to increase plasma OT levels did not differ from that of naloxone. Injected i.c.v., neither methyl naloxone nor naloxone had a clear effect and they antagonized i.c.v. co-administered dynorphin A-(1-13) equipotently. Methyl naloxone or naloxone, s.c., antagonized the inhibitory action of simultaneous dynorphin A-(1-13) and beta-endorphin-(1-31) given i.c.v., although higher doses of methyl naloxone were required. The data indicate that the sites of inhibition of neurohypophysial hormone release due to beta-endorphin-(1-31) are more likely to be located mostly within the blood-brain barrier, to which methyl naloxone has less ready access, than are the sites of inhibition due to dynorphin A-(1-13).
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PMID:Pharmacological assessment of the site of action of opioids on the release of vasopressin and oxytocin in the rat. 168 Jul 8

The neurointermediate lobe of the pituitary (NIL) contains the opioid peptides methionine enkephalin (MENK) and dynorphin 1-8 (DYN) in addition to oxytocin (OT) and vasopressin (AVP). If the opioids have a functional role, such as feedback control on OT or AVP release, the content or release of the opioids might be expected to change under conditions in which OT or AVP change. This expectation was examined by studying the synthesis, storage and release of the 4 peptides under conditions in which OT and AVP dynamics are known to be altered. Diestrus, diethylstilbesterol(DES)-treated, and day 22 pregnant rats were decapitated, the hypothalamo-neurohypophysial system (HNS) excised and either superfused in oxygenated Krebs buffer at 37 degrees C or stored at -80 degrees C for measurement of paraventricular and supraoptic nuclei mRNA content by in situ hybridization analysis. Peptide content of superfusates and NIL homogenates were determined by specific RIAs. Compared with diestrus animals, DES treatment increased NIL OT but decreased MENK. In term pregnant rats, NIL OT, AVP, and DYN were increased over diestrus values, while MENK was again decreased. Release of the peptides from the isolated HNS paralleled changes in NIL content. The hypothalamic mRNA for OT was increased in DES-treated and pregnant rats while MENK mRNA was decreased. AVP and DYN mRNA was increased in pregnant animals. Although the NIL was found to contain much more immunoreactive OT and AVP than MENK or DYN, under basal conditions the release of MENK was equal to or greater than the release of OT, while the release of DYN approached that of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diethylstilbesterol- and pregnancy-induced changes in rat neurointermediate lobe oxytocin, arginine vasopressin, methionine enkephalin and dynorphin. 168 32

In situ hybridization histochemistry and indirect immunofluorescence histochemistry were used to study changes in the expression of vasopressin (VP), oxytocin (OXY), tyrosine hydroxylase (TH), galanin (GAL), dynorphin (DYN) and cholecystokinin (CCK) in hypothalamic magnocellular neurons of the paraventricular (PVN) and supraoptic (SON) nuclei of rats. After prolonged administration of 2% sodium chloride as drinking water (salt-loading), the treatment increased the levels of VP, OXY, TH, GAL, DYN and CCK mRNA in the PVN and SON. The increase in CCK mRNA was, however, proportionally higher in the PVN than in the SON. Within cell bodies of the PVN and SON of salt-loaded rats, a depletion of VP- and OXY-like immunoreactivity (LI) and an increase in TH-LI were seen. In salt-loaded/colchicine-treated rats, a marked decrease in GAL- and DYN-LI, but no specific changes in CCK-LI were observed. Within nerve fibers of the posterior pituitary of salt-loaded rats, a marked depletion of VP-, GAL- and DYN-LI was found. Less pronounced depletion was observed in OXY- and CCK-LI, and no specific changes in TH-LI were seen. The results show that high plasma osmolality induces increased mRNA levels for VP, OXY, TH, GAL, DYN and CCK, presumably indicating increased synthesis, an increased export from cell somata of VP, OXY, GAL and DYN, and a decrease in levels of these peptides in the posterior pituitary, suggesting increased release. The catecholamine-synthesizing enzyme TH, however, which has a cytoplasmic localization and is not released from nerve endings, remains high in the cell bodies and nerve endings during this state of increased activity.
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PMID:Peptides and transmitter enzymes in hypothalamic magnocellular neurons after administration of hyperosmotic stimuli: comparison between messenger RNA and peptide/protein levels. 169 5


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