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 effect of NG-nitro-L-arginine methyl ester (NAME), a potent inhibitor of nitric oxide (NO) synthase, injected into different brain areas on penile erection and yawning induced by apomorphine or oxytocin was studied in male rats. The compound was found to be able to prevent the above behavioral responses dose dependently when injected into the paraventricular nucleus of the hypothalamus (PVN), but not in the caudate nucleus, medial septum, preoptic area, and the CA1 field of the hippocampus. When injected in the PVN, 5 micrograms of NAME induced a 30% reduction of apomorphine and oxytocin responses, while 20 micrograms induced an almost complete reduction. The effect of NAME seems to be related to the inhibition of guanylate cyclase secondary to the prevention of NO formation, because a dose-dependent reduction of apomorphine and oxytocin responses was obtained also with the inhibitor of guanylate cyclase methylene blue injected intracerebroventricularly (100-400 micrograms ICV), but not into the PVN. The results provide further support for a neurotransmitter role of central NO in the control of penile erection and yawning.
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PMID:Prevention by NG-nitro-L-arginine methyl ester of apomorphine- and oxytocin-induced penile erection and yawning: site of action in the brain. 793 38

In order to investigate the mechanism of action by which oxytocin induces penile erection, the effect of NG-nitro-L-arginine methyl ester (NAME) and NG-monomethyl-L-arginine (NMMA), inhibitors of nitric oxide (NO) synthase, injected into the paraventricular nucleus of the hypothalamus (PVN) on the response to oxytocin injected into the PVN was studied in male rats. NAME and NMMA, but not NG-mono-methyl-D-arginine (D-NMMA), which does not inhibit NO-synthase, prevented in a dose-dependent manner the response to oxytocin. NAME was 4-5 times more potent than NMMA. NAME prevention of the oxytocin effect was not observed when NAME was given together with L-arginine but not with D-arginine. Oxytocin-induced penile erection was prevented by the oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-vasotocin and by methylene blue, an inhibitor of guanylate cyclase, but not reduced hemoglobin, a NO scavenger, given intracerebroventricularly (i.c.v.). In contrast, both methylene blue and hemoglobin were ineffective when injected into the PVN, unlike d(CH2)5Tyr(Me)-Orn8-vasotocin. Penile erection was induced also by sodium nitroprusside and hydroxylamine, two NO donors, injected into the PVN. Like the oxytocin effect, the NO donor response was prevented by i.c.v. d(CH2)5Tyr(Me)-Orn8-vasotocin and methylene blue, but not hemoglobin. In contrast, the three compounds were ineffective in preventing the NO donor response when injected into the PVN. The present results suggest that oxytocin induces penile erection by activating NO synthase in the PVN. NO in turn activates oxytocinergic neurons projecting to extra-hypothalamic areas that control the expression of this male sexual function by a guanosine cyclic 3':5'-monophosphate (cGMP) independent mechanism at least in the PVN.
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PMID:Oxytocin-induced penile erection. Role of nitric oxide. 871 73

A low dose of apomorphine (80 micrograms/kg s.c.), a mixed D1/D2 agonist that induces penile erection and yawning, increased the concentration of NO2-from 1.12 +/- 0.45 microM to 3.8 +/- 0.75 microM and NO3-from 5.53 +/- 0.82 to 11.25 +/- 2.30 microM in the dialysate collected from the paraventricular nucleus of the hypothalamus of male rats by in vivo microdialysis. The NO2-concentration was also increased by LY 171555 (50 micrograms/kg s.c.), a D2 agonist that induces penile erection and yawning, but not by SKF 38393 (5 mg/kg s.c.), a D1 agonist with no effect on these responses. Conversely, apomorphine's effect on NO2-was prevented by haloperidol (0.5 mg/kg i.p.), a mixed D1/D2 antagonist and L-sulpiride (25 mg/kg i.p.), a D2 antagonist, but not by the D1 agonist SCH 23390 (50 micrograms/kg s.c.), although all three compounds prevented penile erection and yawning. The apomorphine effect on NO2-, penile erection and yawning was also prevented by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (200 micrograms i.c.v.). The nitric oxide scavenger haemoglobin (200 micrograms i.c.v.) also prevented the NO2-increase, but was ineffective against penile erection and yawning. In contrast, the oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-vasotocin (1 microgram i.c.v.) and the guanylate cyclase inhibitor methylene blue (300 micrograms i.c.v.) had no effect on the NO2-increase, but did prevent the behavioural responses. We infer from this that dopamine agonists induce penile erection and yawning by acting on D2 receptors that increase nitric oxide synthase activity in the cell bodies of paraventricular oxytocinergic neurons projecting to extra-hypothalamic brain areas.
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PMID:Dopamine agonists increase nitric oxide production in the paraventricular nucleus of the hypothalamus: correlation with penile erection and yawning. 892 Dec 95

Atrial natriuretic peptide (ANP) and its receptors are present in hypothalamic nuclei containing the magnocellular neurosecretory cells (MNCs), which release vasopressin and oxytocin. In the rat, intracerebroventricular injections of ANP inhibit the release of both hormones in response to hypertonicity. Although these findings suggest a role for endogenous ANP in the central control of fluid balance, cellular mechanisms underlying the modulatory actions of ANP are unknown. We therefore examined the effects of ANP on the osmoresponsiveness of MNCs impaled in rat hypothalamic explants. Applications of ANP (75-150 nM) over the supraoptic nucleus did not affect depolarizing responses to local hypertonicity, but they reversibly abolished the synaptic excitation of MNCs after hypertonic stimulation of the organum vasculosum laminae terminalis (OVLT). These effects were associated with decreased spontaneous EPSP (sEPSP) amplitude rather than with changes in sEPSP frequency. Accordingly, application of ANP reduced the amplitude of glutamatergic EPSPs evoked by electrical stimulation of the OVLT (IC50 approximately 3 nM). The inhibitory effects of ANP on EPSP amplitude were mimicked by application of 3'-5'-dibutyryl cGMP, consistent with the guanylate cyclase activity of natriuretic peptide receptors. Although depolarizing responses of MNCs to ionotropic glutamate receptor agonists were unaffected by ANP, the peptide reversibly enhanced paired-pulse facilitation of electrically evoked EPSPs. These results indicate that centrally released ANP may inhibit osmotically evoked neurohypophysial hormone release through presynaptic inhibition of glutamate release from osmoreceptor afferents derived from the OVLT.
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PMID:Atrial natriuretic peptide modulates synaptic transmission from osmoreceptor afferents to the supraoptic nucleus. 892 8

A dose of oxytocin (50 ng i.c.v.) that induces penile erection and yawning, increased the concentration of NO2- from 0.98 +/- 0.29 to 4.2 +/- 0.79 microM and of NO3- from 5.6 +/- 0.33 to 12.03 +/- 0.99 microM in the dialysate from the paraventricular nucleus of the hypothalamus of male rats, as measured by in vivo microdialysis. NO2- concentration was also increased by [Thr4, Gly7]-oxytocin (100 ng i.c.v. and oxytocin(8) (1 microgram i.c.v.) which also induced penile erection and yawning, but not by oxytocin(1-6) (1 microgram i.c.v.) or oxytocin (7-9) 1 microgram i.c.v.), which were unable to induce these behavioral responses. The oxytocin effect on NO2 concentration, penile erection and yawning was prevented by the oxytocin receptor antagonist. d(CH2)5,Tyr(Me)-Orn8-vasotocin (1 microgram i.e.v.) or by the nitric oxide synthase inhibitor, NG-nitro-1-arginine methyl ester (200 micrograms i.c.v.), but not by the dopamine receptor antagonist, haloperidol (0.5 mg/kg i.p.). The nitric oxide scavenger, hemoglobin (200 micrograms i.c.v.), prevented oxytocin-induced NO2- concentration increase, but was unable to prevent penile erection and yawning. Methylene blue (300 micrograms i.c.v.) an inhibitor of guanylate cyclase, was ineffective on oxytocin-induced NO2- concentration increase, but prevented the behavioral responses. The results suggest that oxytocin induces penile erection and yawning by increasing nitric oxide synthase activity in the cell bodies of oxytocinergic neurons projecting to extra-hypothalamic brain areas and mediating the behavioral responses.
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PMID:Oxytocin increases nitric oxide production in the paraventricular nucleus of the hypothalamus of male rats: correlation with penile erection and yawning. 917 53

1. Recent experimental evidence has shown that nitric oxide (NO) plays an important role in the expression of penile erection and yawning and that this molecule has to be added to the list of the best known neurotransmitters and neuropeptides involved in this symptomatology. 2. This was first suggested by the ability of NO synthase inhibitors injected in the lateral ventricles (i.c.v.) or in the paraventricular nucleus of the hypothalamus (PVN) to prevent these behavioral responses induced by dopamine agonists, oxytocin and NMDA. The inhibitory effect of NO synthase inhibitors was not observed when these compounds were injected concomitantly with L-arginine, the precursor of NO. Most important, this hypothalamic nucleus is one of the richest brain areas of NO synthase and also the brain site where dopamine, NMDA and oxytocin act to induce penile erection and yawning by activating central NO synthase containing oxytocinergic neurons. 3. NO synthase inhibitors given i.c.v. but not in the PVN prevent also penile erection and yawning induced by ACTH and serotonin1c agonists, which induce these responses by acting with mechanisms unrelated to oxytocinergic transmission. 4. Dopamine agonists, NMDA and oxytocin increase NO production in the PVN at doses that induce penile erection and yawning, as determined by measuring the concentration of NO2- and NO3- in the dialyzate obtained with a vertical probe implanted in the PVN by in vivo microdialysis. 5. NO donors, such as nitroglycerin, sodium nitroprusside and hydroxylamine, induce penile erection and yawning indistinguishable from those induced by oxytocin, dopamine agonists or NMDA when injected in the PVN. The NO donor response was prevented by the i.c.v. injection of the oxytocin receptor antagonist d(CH2)5-Tyr(Me)-Orn8-vasotocin, indicating that these compounds also induce penile erection and yawning by activating oxytocinergic transmission. 6. Finally, guanylate cyclase inhibitors (i.e. methylene blue and LY 83583) and hemoglobin injected in the PVN do not prevent drug-induced penile erection and yawning, nor 8-Br-cGMP injected in the PVN induces these behavioral responses suggesting that the mechanism by means of which endogenous or NO donor-derived NO facilitates oxytocinergic transmission to induce penile erection and yawning is not related to the activation of guanylate cyclase. Furthermore, since hemoglobin, in spite of its ability to prevent drug-induced NO production in the PVN, does not prevent penile erection and yawning, it is likely that NO acts as an intracellular rather than an intercellular modulator in the PVN neurons in which is formed to facilitate the expression of these behavioral responses.
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PMID:Role of central nitric oxide in the control of penile erection and yawning. 938 Jul 88

Neurons containing neural nitric oxide synthase (nNOS) are found in various locations in the hypothalamus and, in particular, in the paraventricular and supraoptic nuclei with axons which project to the median eminence and extend into the neural lobe where the highest concentrations of NOS are found in the rat. Furthermore, nNOS is also located in folliculostellate cells and LH gonadotropes in the anterior pituitary gland. To define the role of NO in the release of hypothalamic peptides and pituitary hormones, we injected an inhibitor of NOS, Ng-monomethyl-L-arginine (NMMA) or a releasor of NO, nitroprusside (NP) into the third ventricle (3V) of conscious castrate rats and determined the effect on the release of various pituitary hormones. In vitro, we incubated medial basal hypothalamic (MBH) fragments and studied inhibitors of NO synthase and also releasors of NO. The results indicate that NOergic neurons play an important role in stimulating the release of corticotrophin-releasing hormone (CRH), luteinizing hormone releasing-hormone (LHRH), prolactin-RH's, particularly oxytocin, growth hormone-RH (GHRH) and somatostatin, but not FSH-releasing factor from the hypothalamus. NO stimulates the release of LHRH, which induces sexual behavior, and causes release of LH from the pituitary gland. The intrahypothalamic pathway by which NO controls LHRH release is as follows: glutamergic neurons synapse with noradrenergic terminals in the MBH which release nonepinephrine (NE) that acts on alpha 1 receptors on the NOergic neuron to increase intracellular free Ca++ which combines with calmodulin to activate NOS. The NOS diffuses to the LHRH terminal and activates guanylate cyclase (GC), cyclooxygenase and lipoxygenase causing release of LHRH via release of cyclic GMP, PGE2 and leukotrienes, respectively. Alcohol and cytokines can block LHRH release by blocking the activation of cyclooxygenase and lipoxygenase without interfering with the activation of GC. GABA also blocks the response of the LHRH neurons to NO and recent experiments indicate that granulocyte macrophage colony-stimulating factor (GMCSF) blocks the response of the LHRH neuron to NP by activation of GABA neurons since the blockade can be reversed by the competitive inhibitor of GABAa receptors, bicuculine.
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PMID:The role of nitric oxide (NO) in control of hypothalamic-pituitary function. 939 93

Gonadotropin secretion by the pituitary gland is under the control of luteinizing hormone-releasing hormone (LHRH) and the putative follicle-stimulating hormone-releasing factor (FSHRF). Lamprey III LHRH is a potent FSHRF in the rat and appears to be resident in the FSH controlling area of the rat hypothalamus. It is an analog of mammalian LHRH and may be the long-sought FSHRF. Gonadal steroids feedback at hypothalamic and pituitary levels to either inhibit or stimulate the release of LH and FSH, which is also affected by inhibin and activin secreted by the gonads. Important control is exercised by acetylcholine, norepinephrine (NE), dopamine, serotonin, melatonin and glutamic acid (GA). Furthermore, LH and FSH also act at the hypothalamic level to alter secretion of gonadotropins. More recently, growth factors have been shown to have an important role. Many peptides act to inhibit or increase release of LH, and the sign of their action is often reversed by estrogen. A number of cytokines act at the hypothalamic level to suppress acutely the release of LH but not FSH. NE, GA and oxytocin stimulate LHRH release by activation of neural nitric oxide synthase (nNOS). The pathway is as follows: oxytocin and/or GA activate NE neurons in the medial basal hypothalamus (MBH) that activate NOergic neurons by alpha1 receptors. The NO released diffuses into LHRH terminals and induces LHRH release by activation of guanylate cyclase (GC) and cyclooxygenase. NO not only controls release of LHRH bound for the pituitary, but also that which induces mating by actions in the brain stem. An exciting recent development has been the discovery of the adipocyte hormone, leptin, a cytokine related to tumor necrosis factor-alpha (TNF-alpha). In the male rat, leptin exhibits a high potency to stimulate FSH and LH release from hemipituitaries incubated in vitro, and increases the release of LHRH from MBH explants by stimulating the release of NO. LHRH and leptin release LH by activation of NOS in the gonadotropes. The NO released activates GC that releases cyclic GMP which induces LH release. Leptin induces LH release in conscious, ovariectomized estrogen-primed female rats, presumably by stimulating LHRH release. At the effective dose of estrogen to activate LH release, FSH release is inhibited. Leptin may play an important role in induction of puberty and control of LHRH release in the adult as well.
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PMID:Hypothalamic control of FSH and LH by FSH-RF, LHRH, cytokines, leptin and nitric oxide. 973 Jun 86

Gonadotropin secretion by the pituitary gland is under the control of luteinizing hormone-releasing hormone (LHRH) and the putative follicle stimulating hormone-releasing factor (FSHRF). Lamprey III LHRH is a potent FSHRF in the rat and seems to be resident in the FSH controlling area of the rat hypothalamus. It is an analog of mammalian LHRH and may be the long sought FSHRF. Gonadal steroids feedback at hypothalamic and pituitary levels to either inhibit or stimulate the release of LH and FSH, which is also affected by inhibin and activin secreted by the gonads. Important control is exercised by acetylcholine, norepinephrine (NE), dopamine, serotonin, melatonin, and glutamic acid (GA). Furthermore, LH and FSH also act at the hypothalamic level to alter secretion of gonadotropins. More recently, growth factors have been shown to have an important role. Many peptides act to inhibit or increase release of LH and the sign of their action is often reversed by estrogen. A number of cytokines act at the hypothalamic level to suppress acutely the release of LH but not FSH. NE, GA, and oxytocin stimulate LHRH release by activation of neural nitric oxide synthase (nNOS). The pathway is as follows: oxytocin and/or GA activate NE neurons in the medial basal hypothalamus (MBH) that activate NOergic neurons by alpha, (alpha 1) receptors. The NO released diffuses into LHRH terminals and induces LHRH release by activation of guanylate cyclase (GC) and cyclooxygenase. NO not only controls release of LHRH bound for the pituitary, but also that which induces mating by actions in the brain stem. An exciting recent development has been the discovery of the adipocyte hormone, leptin, a cytokine related to tumor necrosis factor (TNF) alpha. In the male rat, leptin exhibits a high potency to stimulate FSH and LH release from hemipituitaries incubated in vitro, and increases the release of LHRH from MBH explants. LHRH and leptin release LH by activation of NOS in the gonadotropes. The NO released activates GC that releases cyclic GMP, which induces LH release. Leptin induces LH release in conscious, ovariectomized estrogen-primed female rats, presumably by stimulating LHRH release. At the effective dose of estrogen to activate LH release, FSH release is inhibited. Leptin may play an important role in induction of puberty and control of LHRH release in the adult as well.
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PMID:Hypothalamic control of gonadotropin secretion by LHRH, FSHRF, NO, cytokines, and leptin. 978 37

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


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