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)

Although prostaglandin (PG) F(2alpha) released from the uterus has been shown to cause regression of the bovine corpus luteum (CL), the neuroendocrine, paracrine, and autocrine mechanisms regulating luteolysis and PGF(2alpha) action in the CL are not fully understood. A number of substances produced locally in the CL may be involved in maintaining the equilibrium between luteal development and its regression. The present study was carried out to determine whether noradrenaline (NA) and nitric oxide (NO) regulate the sensitivity of the bovine CL to PGF(2alpha) in vitro and modulate a positive feedback cascade between PGF(2alpha) and luteal oxytocin (OT) in cows. Bovine luteal cells (Days 8-12 of the estrous cycle) cultured in glass tubes were pre-exposed to NA (10(-5) M) or an NO donor (S-nitroso-N:-acetylpenicillamine [S-NAP]; 10(-4) M) before stimulation with PGF(2alpha) (10(-6) M). Noradrenaline significantly stimulated the release of progesterone (P(4)), OT, PGF(2alpha), and PGE(2) (P: < 0.01); however, S-NAP inhibited P(4) and OT secretion (P: < 0.05). Oxytocin secretion and the intracellular level of free Ca(2+) ([Ca(2+)](i)) were measured as indicators of CL sensitivity to PGF(2alpha). Prostaglandin F(2alpha) increased both the amount of OT secretion and [Ca(2+)](i) by approximately two times the amount before (both P: < 0.05). The S-NAP amplified the effect of PGF(2alpha) on [Ca(2+)](i) and OT secretion (both P: < 0.001), whereas NA diminished the stimulatory effects of PGF(2alpha) on [Ca(2+)](i) (P: < 0.05). Moreover, PGF(2alpha) did not exert any additionally effects on OT secretion in NA-pretreated cells. The overall results suggest that adrenergic and nitrergic agents play opposite roles in the regulation of bovine CL function. While NA stimulates P(4) and OT secretion, NO may inhibit it in bovine CL. Both NA and NO are likely to stimulate the synthesis of luteal PGs and to modulate the action of PGF(2alpha). Noradrenaline may be the factor that is responsible for the limited action of PGF(2alpha) on CL and may be involved in the protection of the CL against premature luteolysis. In contrast, NO augments PGF(2alpha) action on CL and it may be involved in the course of luteolysis.
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PMID:Influence of nitric oxide and noradrenaline on prostaglandin F(2)(alpha)-induced oxytocin secretion and intracellular calcium mobilization in cultured bovine luteal cells. 1099 20

Reflexive erection initiated by recruitment of penile afferents, involves both autonomic and somatic efferents. The reflex is mediated at the spinal cord level, modulated by supraspinal influences, and may use several transmitters. Dopamine, acetylcholine, nitric oxide, and peptides, such as oxytocin and ACTH/alpha-MSH, seem to have a facilitatory role, whereas serotonin may be either facilitatory or inhibitory, and enkephalins are inhibitory. Peripherally, the balance between contractant and relaxant factors controls the degree of contraction of the smooth muscle of the corpora cavernosa, and determines the functional state of the penis. Noradrenaline contracts both corpus cavernosum and penile vessels via stimulation of alpha1-adrenoceptors. The role of endothelins in the control of penile smooth muscle tone is presently unclear. Neurogenic nitric oxide (NO) is considered the most important factor for relaxation of penile vessels and corpus cavernosum. The role of other mediators, released from nerves or endothelium has not been definitely established. International Journal of Impotence Research (2000) 12, Suppl 4, S26-S33.
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PMID:Neurotransmitters: central and peripheral mechanisms. 1103 83

Oxytocin secretion is important for the normal progress of parturition in the rat. We tested the hypotheses that contractions of the uterus before pup delivery activate oxytocin neurons, and that they do so via a noradrenergic projection. In anesthetized 22-day (term) pregnant rats, i.v. oxytocin pulses enhanced both uterine contractile activity and the firing rate of oxytocin and vasopressin neurons in the supraoptic nucleus, and these were significantly correlated. The same oxytocin treatment also increased the expression of Fos in both the supraoptic nucleus and the nucleus of the tractus solitarius, but not in 21-day pregnant or virgin rats. In five of eight rats on the day of expected parturition, noradrenaline release in the supraoptic nucleus (sampled by microdialysis) exhibited sudden peaks during oxytocin administration, seen in only one of nine rats given vehicle pulses. Noradrenaline release was significantly greater in rats that went into labor or gave birth to a pup than in rats not in labor. In rats infused with the alpha(1)-noradrenergic receptor antagonist, benoxathian, into the supraoptic nucleus before and during iv oxytocin administration, Fos expression in supraoptic neurons was significantly less than that in vehicle controls. Thus, at term pregnancy, uterine contractions activate both oxytocin and vasopressin neurons in the SON, and this activation involves a noradrenergic pathway.
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PMID:Uterine contractile activity stimulates supraoptic neurons in term pregnant rats via a noradrenergic pathway. 1115 34

Noxious stimuli facilitate oxytocin release from the pituitary. Oxytocin cells receive excitatory synaptic inputs from the noradrenergic neurones located in the medulla oblongata. Oxytocin release after noxious stimuli is blocked by noradrenaline depletion in the brain. Here, we examined effects of noxious stimuli upon noradrenaline release within the supraoptic nucleus. Electric footshocks or mustard oil application to the foot pad facilitated noradrenaline release in the nucleus. Noradrenaline release after noxious stimuli was impaired by microinjections with a GABA(A) receptor agonist, muscimol, or an alpha 2 adrenoceptor agonist, clonidine, into the A1 noradrenergic cell regions. From these and reported data, we conclude that the medullary A1 noradrenergic neurones contribute, at least in part, to oxytocin release from the pituitary after noxious stimuli.
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PMID:Medullary A1 noradrenergic neurones may mediate oxytocin release after noxious stimuli. 1149 37

Erection is basically a spinal reflex that can be initiated by recruitment of penile afferents, but also by visual, olfactory, and imaginary stimuli. The reflex involves both autonomic and somatic efferents and is modulated by supraspinal influences. Several central transmitters involved in the erectile control have been identified. Dopamine, acetylcholine, nitric oxide (NO), and peptides, such as oxytocin and adrenocorticotropic/alpha-melanocyte-stimulating hormone, seem to have a facilitatory role, whereas serotonin may be either facilitatory or inhibitory, and enkephalins are inhibitory. Peripherally, the balance between contractant and relaxant factors controls the degree of contraction of the smooth muscle of the corpora cavernosa and determines the functional state of the penis. Noradrenaline contracts both corpus cavernosum and penile vessels via stimulation of alpha(1)-adrenoceptors. Neurogenic NO is considered the most important factor for relaxation of penile vessels and corpus cavernosum. The role of other mediators released from nerves or endothelium has not been definitely established. Erectile dysfunction (ED) may be due to inability of penile smooth muscles to relax. This inability can have multiple causes. However, patients with ED respond well to the pharmacological treatments that are currently available. The drugs used are able to substitute, partially or completely, the malfunctioning endogenous mechanisms that control penile erection. Most drugs have a direct action on penile tissue facilitating penile smooth muscle relaxation, including prostaglandin E(1), NO donors, phosphodiesterase inhibitors, and alpha-adrenoceptor antagonists. Dopamine receptors in central nervous centers participating in the initiation of erection have been targeted for the treatment of ED. Apomorphine, administered sublingually, is the first of such drugs.
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PMID:Pharmacology of penile erection. 1154 36

1. We investigated whether catecholamines through activation of alpha(1)-adrenergic receptors (alpha(1)-AR) are involved in mouse uterine contraction at parturition. Myometrial phospholipase C (PLC) activity and uterine contraction were measured in response to noradrenaline (NA), the specific alpha(1)-AR agonist phenylephrine (Phe) and oxytocin (OT). 2. Using the reverse transcription-polymerase chain reaction RT-PCR, we detected the alpha(1a)-AR subtype in late pregnant mouse myometrium. We also detected, by immunoblotting studies, PLCbeta(1), PLCbeta(3) and different alpha-subunits of pertussis toxin-insensitive (Galpha(q/11)) and -sensitive G proteins (Galpha(o/i3), Galpha(i1/2)). 3. Phenylephrine and NA did not alter the myometrial inositol phosphate (InsP) production of late pregnant or parturient mouse. In similar conditions, OT increased InsP production in a dose-dependent manner. Consistent with these results, only OT (10 microM) recruited PLCbeta(1) and PLCbeta(3) to myometrial plasma membranes. The OT-induced InsP response was not altered by pertussis toxin (300 ng ml(-1), 2 h pretreatment), suggesting the involvement of a member of the Galpha(q) family. 4. Noradrenaline and Phe failed to increase uterine contraction at late pregnancy and at parturition. In contrast, OT induced uterine contraction in a dose-dependent manner with maximal increase (400 %) at a concentration of 1 microM. 5. The results indicate that OT receptors (OTR) but not alpha(1)-AR are linked to myometrial PLC activation and uterine contraction in late pregnant and parturient mouse. This discrepancy between mouse and other mammals could be attributed to the alpha(1)-AR subtype expressed in myometrium at this time.
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PMID:Catecholamines are not linked to myometrial phospholipase C and uterine contraction in late pregnant and parturient mouse. 1157 62

Noradrenaline and serotonin are known to control arginine-vasopressin (AVP) and oxytocin (OT) secretion in the systemic circulation. The aim of the current study was to investigate whether these monoamines are also able to influence AVP and OT expression in the paraventricular (PVN) and supraoptic nuclei (SON). To test this hypothesis, we used the Tg8 transgenic mice KO for the monoamine oxidase-A gene, which present high levels of noradrenaline and serotonin in the brain. AVP and OT expression were evaluated at peptide and mRNA levels by immunohistochemistry, enzyme immunoassay, and in situ hybridization. Compared with wild type, the amounts of AVP, OT, AVP mRNA, and OT mRNA were increased in the PVN and SON in Tg8 mice. To distinguish the respective contributions of noradrenaline and serotonin to these modifications, we treated Tg8 mice with a synthesis inhibitor of either catecholamines [alpha-methylparatyrosine (alpha-MPT)] or serotonin [parachlorophenylalanine (pCPA)]. Administration of alpha-MPT to Tg8 mice induced a decline in the amounts of AVP, OT, and their mRNA in the PVN and SON. The pCPA treatment in Tg8 mice was also associated with a decrease in OT expression in the PVN and SON and in AVP expression in the PVN, but not in the SON. These results suggest that noradrenaline may activate AVP and OT expression in the PVN and SON. Likewise, serotonin is proposed to stimulate AVP and OT expression in the PVN and only OT expression in the SON.
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PMID:Activation by serotonin and noradrenaline of vasopressin and oxytocin expression in the mouse paraventricular and supraoptic nuclei. 1188 Apr 81

The regulation of aquaporin-2 (AQP2) water channel excretion in the collecting duct depends mainly on the action of vasopressin (AVP). Recently, however, other regulatory factors have been identified: atrial natriuretic factor, oxytocin and prostaglandins. In healthy volunteers (5 males, 5 females; mean age 23 +/- 3 years) we therefore evaluated the effect of a stable analogue of prostacyclin-2 (PGI(2)), iloprost, on renal function and on the urinary excretion of AQP2 (U-AQP2). After 6 h of iloprost infusion, U-AQP2 increased from 0.8 +/- 0.15 to 1.8 +/- 0.2 pmol/mg creatinine (p < 0.001), while the urinary flow rate increased from 1.4 +/- 0.2 to 1.8 +/- 4 (p < 0.01). No significant change was found in the AVP serum concentration, with a basal value of 3.17 +/- 0.12 vs. 3.15 +/- 0.12 pg/ml after 6 h of prostacyclin infusion. All the values returned to pre-study levels after a recovery period of 6 h. In conclusion, the PGI(2) analogue, iloprost, can induce U-AQP2 excretion independent of AVP.
Nephron 2002 Jun
PMID:Effect of a prostacyclin analogue, iloprost, on urinary aquaporin-2 excretion in humans. 1205 53

Antidepressants rapidly relieve pain in irritable bowel syndrome (IBS) and are effective at low doses. Noradrenaline reuptake inhibitors appear to be more effective than selective serotonergic reuptake inhibitors, suggesting that pathways other than those modulated by serotonin may be involved in visceral sensation. Visceral sensitivity is reduced by both centrally and peripherally acting opioids, suggesting the possible existence of an endogenous opioid deficiency in patients with IBS. The alpha(2) adrenoceptor antagonist clonidine, as well as somatostatin, oxytocin, and possibly amitriptyline have also been shown to act as visceral analgesics. As knowledge increases, there are undoubtedly many other possible targets, and new drugs currently undergoing development may provide future benefit in patients with IBS.
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PMID:Pharmacotherapy: non-serotonergic mechanisms. 1207 75

The aquaporin-2 (AQP2) water channel is mainly located in the apical plasma membrane of collecting duct epithelial cells, but there has been some evidence of a moderate amount of basolateral localization of AQP2 at least in the inner medullary collecting duct (IMCD). Previous in vitro microperfusion studies showed that oxytocin has an antidiuretic action, most likely mediated by the vasopressin V2 receptor (V2R) in rat IMCD. By using immunohistochemistry in kidneys from male Sprague-Dawley rats, we observed acute effects of oxytocin on AQP2 localization which were prevented by a V2R antagonist. After intraperitoneal administration of oxytocin (10 U), immunohistochemistry of IMCD revealed that AQP2 was shifted from diffuse cytoplasmic localization in controls to the apical and basolateral membrane domains in oxytocin-treated rats. This pattern of AQP2 redistribution was noted in connecting tubule, cortical collecting duct and outer medullary collecting duct as well as in IMCD, although the tendency to basolateral localization was somewhat less. The pretreatment using a V2R antagonist blocked redistribution of AQP2 in response to oxytocin. We conclude that oxytocin induces a V2R-mediated redistribution of AQP2-containing cytoplasmic vesicles to both apical and basolateral plasma membrane domains in rat kidney. Oxytocin may be one of the factors that accounts for vasopressin-independent AQP2 targeting in the kidney.
Nephron Exp Nephrol 2003 Jan
PMID:Oxytocin induces apical and basolateral redistribution of aquaporin-2 in rat kidney. 1241 48


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