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)

Neurokinin A (NKA) is a tachykinin that participates in the control of neuroendocrine functions. The posterior pituitary lobe (PP) contains abundant nitric oxide synthase (NOS), suggesting that nitric oxide (NO) may play a role in controlling the release of neuropeptides and neurotransmitters. In the present project, we investigated the in vitro effect of NKA on oxytocin release from hypothalamic explants and PP of male rats and the possible involvement of NO in the action of NKA. Since NKA inhibits gamma-aminobutyric acid (GABA) release from PP, we also examined the role of NO in the effect of NKA on basal and K(+)-evoked GABA release. NKA (10(-7)-10(-5) M) significantly decreased oxytocin release from PP, whereas it did not affect its release from hypothalamic explants. The inhibitory effect of NKA on oxytocin release from PP was completely blocked by the NOS inhibitors N(G)-monomethyl-L-arginine (L-NMMA, 0.5 mM) or N(G)-nitro-L-arginine-methyl-ester (L-NAME, 1 mM). Sodium nitroprusside (0.5 mM), an NO releaser, had no effect on basal GABA release but significantly decreased K(+)-evoked GABA release. L-NMMA (0.3 mM) and L-NAME (0.5 mM) increased K(+)-evoked GABA release, indicating that NO plays an inhibitory role in GABA release from PP. The inhibition in both basal and K(+)-evoked GABA release induced by NKA (10(-7) M) was reduced by L-NAME (1 mM). Also, NKA (10(-7) M) increased NO synthesis as measured by [(14)C] citrulline production. Considered all together, our data indicate that NO may mediate the inhibitory effect of NKA on the release of both oxytocin and GABA from PP.
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PMID:Neurokinin A inhibits oxytocin and GABA release from the posterior pituitary by stimulating nitric oxide synthase. 1111 87

The gas nitric oxide is a messenger in brain signaling. In the hypothalamo-hypophyseal system nitric oxide is involved in the control of the expression and/or release of peptide hormones (corticotropin-releasing hormone, gonadotropin-releasing hormone, vasopressin and oxytocin). Nitric oxide synthase (NOS), the enzyme generating nitric oxide, is abundantly present in the magnocellular nuclei of the rat hypothalamus. Its localization in the human hypothalamus is less well studied. Hence, we investigated the anatomical distribution of neuronal nitric oxide synthase in the human supraoptic nucleus by use of immunohistochemical and enzyme histochemical techniques. The immunohistochemical localization of NOS was studied in 31 matched human hypothalami (13 control cases, eight depressed patients and ten schizophrenics). NADPH-diaphorase studies were carried out on seven additional hypothalami (three normal brains, four schizophrenics). Apparent inter-individual differences exist with regard to the occurrence of the enzyme in supraoptic neurons. In a majority of cases no immunostaining or histochemical reaction for the enzyme was observed. In seven cases (three controls, two schizophrenics, two depressives) a population of nitrergic nerve cells was seen in the dorsomedial part of the nucleus. This group of cells also stained for NADPH-diaphorase. Also, there were a few NOS-immunopositive neurons scattered throughout the nucleus. Additionally, thin NADPH-diaphorase positive fibers were observed to cross the nucleus. Our data show that, unlike the rat, the human supraoptic nucleus contains only a small number of nitrergic neurons. No correlation was found between the expression of the enzyme in supraoptic neurons and the psychiatric status of the patients.
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PMID:Low and infrequent expression of nitric oxide synthase/NADPH-diaphorase in neurons of the human supraoptic nucleus: a histochemical study. 1111 9

To clarify the role of nitric oxide (NO) in the ontogeny of arginine vasopressin (AVP) and oxytocin (OXT) neurons in the hypothalamo-neurohypophysial system (HNS), we observed the coexpression pattern of NADPH-diaphorase (NADPH-d) activity and AVP- or OXT-immunoreactivity (IR) in the rat hypothalamus and posterior pituitary during the postnatal period. The enzymatic activity of NADPH-d was observed in the supraoptic nucleus (SON), paraventricular nucleus (PVN), median eminence (ME) and posterior pituitary throughout the postnatal development. AVP-containing neurons were clearly observed from postnatal day 1 in both the SON and PVN, while OXT-containing neurons were recognized from postnatal day 14. The coexistence of NADPH-d and AVP or OXT was detected in the SON from postnatal day 14. At postnatal day 21, the coexpression pattern was approximately the same as that of the SON and PVN in adult rats. Our findings indicated that the expression of NADPH-d and OXT was observed from almost the same postnatal period in both the SON and PVN. In addition, the pattern of increased numbers of NADPH-d positive fibers was similar to that of OXT-immunoreactive fibers in both the inner layer of the ME and the posterior pituitary. A good correlation was thus obtained between OXT expression and NADPH-d activity in the HNS during postnatal development. The present study suggests that NO is more closely involved in the expression and regulation of secretion of OXT than AVP.
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PMID:Postnatal development of NADPH-diaphorase activity in the rat: the role of nitric oxide in the ontogeny of arginine vasopression and oxytocin. 1120 Sep 42

Yawning is a phylogenetically old, stereotyped event that occurs alone or associated with stretching and/or penile erection in humans, in animals from reptiles to birds and mammals, under different conditions. Several neurotransmitters and neuropeptides are involved in its control at the central level. One of these at the level of the paraventricular hypothalamic nucleus (PVHN) is nitric oxide (NO). First, NO synthase inhibitors injected into this hypothalamic nucleus prevent yawning induced by dopamine agonists, oxytocin or N-methyl-D-aspartic acid (NMDA), which induce yawning by activating PVHN oxytocinergic neurons projecting to extra-hypothalamic brain areas. The inhibitory effect of NO synthase inhibitors was not observed when these compounds were given concomitantly with L-arginine, the precursor of NO. Second, dopamine agonists, NMDA and oxytocin given at doses that induce yawning, increase NO production in the PVHN, as determined by in vivo microdialysis. Conversely, the opiate morphine, which prevents yawning induced by dopamine agonists, oxytocin and NMDA, also prevents the increase in the paraventricular NO production induced by these compounds. Third, NO donors, such as nitroglycerin, sodium nitroprusside and hydroxylamine, induce yawning when injected into the PVHN apparently by activating oxytocinergic transmission. Since guanylate cyclase inhibitors and NO scavengers (hemoglobin) injected into the PVHN do not prevent drug-induced yawning, nor 8-Br-cGMP injected into the PVHN induces this behavioral response, it is likely that NO acts as an intracellular rather than an intercellular modulator inside the PVHN oxytocinergic neurons in which NO is formed to facilitate the expression of this phylogenetically old event by guanylate cyclase-independent mechanisms.
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PMID:Yawning: role of hypothalamic paraventricular nitric oxide. 1124 84

The control of myometrial contractility during pregnancy and parturition is not fully understood. Gas signalling molecules, such as nitric oxide and carbon monoxide, have been shown to relax the myometrium and may be involved in the control of contractility. Hydrogen sulphide has recently been shown to be produced endogenously in animal and human tissue and to have a signalling function. The aim of the study was to investigate the effect of L-cysteine and sodium hydrosulphide, potential hydrogen sulphide donors, on pregnant rat uterine contractility in vitro. Strips of pregnant rat uterus (n=22) were set up in a standard organ bath system. Following equilibration and recording of spontaneous contractility, the tissue was exposed to 45 mM potassium chloride followed by 1 nM oxytocin. Dose ranges of 10(-8) - 10(-3) M of L-cysteine (n=8) or sodium hydrosulphide (n=8) were subsequently applied to the tissue. In a third series of experiments (n=6) the effect of doses of 10(-9), 10(-6) and 10(-3) M of L-cysteine, D-cysteine, L-serine, DL-methionine and DL-homocysteine on myometrial contractility were compared. Contractions were integrated over 10 min. periods and the values were compared by one-way analysis of variance. L-Cysteine and sodium hydrosulphide produced significant dose-dependent decreases in uterine spontaneous contractility. Of the amino acids tested, only L-cysteine produced a significant reduction in spontaneous contractility at a dose of 10(-3) M. This study has demonstrated novel tocolytic actions of L-cysteine and sodium hydrosulphide, however further work is required to determine their mechanisms of action.
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PMID:L-cysteine and sodium hydrosulphide inhibit spontaneous contractility in isolated pregnant rat uterine strips in vitro. 1132 78

The anococcygeus is a smooth muscle tissue of the urogenital tract which, in the male, runs on to form the retractor penis. The motor innervation is classically sympathetic with noradrenaline as transmitter, but the relaxant parasympathetic transmitter has only recently been identified as nitric oxide. Indeed, the anococcygeus has provided an extremely useful model with which to probe the mechanisms underlying this novel nitrergic system, including the importance of physiological antioxidants in maintaining the potency of nitric oxide as a neurotransmitter. The cellular mechanisms of contraction and relaxation are slowly being clarified, with particular interest in the contribution of capacitative calcium entry and the guanylyl cyclase/cyclic GMP system. Many questions remain unanswered, however, including the precise physiological role of the muscle, the identity of substances released from subcellular vesicles of nitrergic nerves, the unusual sensitivity of the tissue to certain peptides (oxytocin and urotensin II), and the nature of store-operated channels through which calcium enters the cell to maintain contraction.
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PMID:Biology of the anococcygeus muscle. 1133 90

To study modulatory actions of nitric oxide (NO) on GABAergic synaptic activity in hypothalamic magnocellular neurons in the supraoptic nucleus (SON), in vitro and in vivo electrophysiological recordings were obtained from identified oxytocin and vasopressin neurons. Whole cell patch-clamp recordings were obtained in vitro from immunochemically identified oxytocin and vasopressin neurons. GABAergic synaptic activity was assessed in vitro by measuring GABA(A) miniature inhibitory postsynaptic currents (mIPSCs). The NO donor and precursor sodium nitroprusside (SNP) and L-arginine, respectively, increased the frequency and amplitude of GABA(A) mIPSCs in both cell types (P < or = 0.001). Retrodialysis of SNP (50 mM) onto the SON in vivo inhibited the activity of both neuronal types (P < or = 0.002), an effect that was reduced by retrodialysis of the GABA(A)-receptor antagonist bicuculline (2 mM, P < or = 0.001). Neurons activated by intravenous infusion of 2 M NaCl were still strongly inhibited by SNP. These results suggest that NO inhibition of neuronal excitability in oxytocin and vasopressin neurons involves pre- and postsynaptic potentiation of GABAergic synaptic activity in the SON.
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PMID:NO inhibits supraoptic oxytocin and vasopressin neurons via activation of GABAergic synaptic inputs. 1135 87

Central regulation of the erectile process involves several transmitters, including dopamine, serotonin, noradrenaline, and nitric oxide, and peptides, such as oxytocin and ACTH/alpha-MSH. These systems may be targets for future drugs designed to treat erectile dysfunction. Peripherally, the different steps involved in neurotransmission, impulse propagation, and intracellular transduction of neural signals in penile smooth muscles need further investigation. Continued studies of the interactions between different transmitters/modulators may reveal new combination therapies. Increased knowledge of the changes in penile tissues associated with erectile dysfunction may explain the pathogenetic mechanisms and help to prevent the disorder.
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PMID:Pharmacology of erectile function and dysfunction. 1140 77

The effect of 10 peptides structurally related to the growth hormone (GH) releasing peptide hexarelin, injected into the paraventricular nucleus of the hypothalamus (PVN), on penile erection was studied in male rats. Six out of the 10 peptides tested induced penile erection in a dose-dependent manner. Among them, the most potent were EP 80661, EP 60761 and EP 91072, which were active at doses of 20-200 ng. The potency of these peptides in inducing penile erection is comparable to that of apomorphine, oxytocin and N-methyl-D-aspartic acid similarly injected into the PVN. Other peptides found active were EP 50885, EP 90101 and EP 91071, which induced penile erection at doses of 200-2000 ng. In contrast, EP 51322, EP 70555, EP 51216 and EP 91073 were inactive, as were hexarelin, EP 40904 and EP 40737 in a previous study. The majority of EP peptides found active when injected into the PVN induced penile erection, although to a lesser extent, also when given systemically (endovenously). The proerectile effect of EP peptides was prevented by the oxytocin receptor antagonist [d(CH2)5 Tyr(Me)2-Orn8]-vasotocin given into the lateral ventricles but not into the PVN, by the nitric oxide (NO) synthase inhibitor N(G)-nitro-1-arginine methyl ester given either into the lateral ventricles or into the PVN, by the N-type Ca2+ channel blocker omega-conotoxin GVIA and by morphine, but not by the dopamine receptor antagonist cis-flupenthixol or by the N-methyl-D-aspartic acid receptor antagonist dizolcipine, given into the PVN. As the structure-activity relationship of EP peptides for proerectile activity is different from those of other biological actions of these compounds, ie for GH release and eating behaviour, the present results suggest that EP peptides induce penile erection by acting on specific hypothalamic receptor sites that activate paraventricular oxytocinergic neurons projecting to extrahypothalamic brain areas that mediate this sexual function by a mechanism similar to that of dopamine receptor agonists, oxytocin and N-methyl-D-aspartic acid.
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PMID:EP 60761- and EP 50885-induced penile erection: structure-activity studies and comparison with apomorphine, oxytocin and N-methyl-D-aspartic acid. 1142 62

Three experiments were carried out to investigate the pattern of neuronal activation induced by central oxytocin administration and its modulation by nitric oxide (NO). First, we compared the induction of Fos-like immunoreactivity (lir) in the supraoptic (SON) and paraventricular (PVN) nuclei and medial preoptic area (MPOA) after central oxytocin administration between nonlactating and lactating rats. Next, we investigated whether NO modulated Fos induction following central oxytocin administration using a nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME). Finally, to determine whether the effects of NOS inhibition on Fos induction would generalize to stimuli other than oxytocin, we compared Fos-lir in the SON and PVN of lactating and nonlactating rats following L-NAME and urethane administration. In the first two experiments, oxytocin (50 ng in 2 microl) or vehicle was administered into the third ventricle. L-NAME (50 mg/kg) was given by an intraperitoneal (i.p.) injection 30 min before oxytocin administration (experiment 2) or an i.p. injection of urethane (1.4 g/kg) (experiment 3). In all experiments, lactating rats were tested on day 12 or 13 postpartum and nonlactating females at least 11 days after surgery or the start of the experiment. Central oxytocin infusion induced Fos expression in the SON and PVN in lactating and nonlactating rats and in the MPOA and bed nucleus of the stria terminalis in lactating rats. Overall, lactating rats that received L-NAME and oxytocin had a greater number of cells showing Fos-lir in both the SON and PVN. Conversely, L-NAME administration reduced Fos-lir in the SON and PVN in oxytocin-stimulated nonlactating rats. In urethane-treated rats, L-NAME administration did not change Fos-lir in lactating rats but reduced Fos-lir in nonlactating rats. These data suggest that the role of NO in modulating the activity of neurones in discrete nuclei in the hypothalamus varies across reproductive state and with the stimulus presented.
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PMID:Effect of nitric oxide synthase inhibition on fos expression in the hypothalamus of female rats following central oxytocin and systemic urethane administration. 1144 74


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