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)

We investigated the distributions and interrelations of neuronal nitric oxide (NO) synthase- (nNOS), oxytocin- (OT), and 8-arginine vasopressin- (AVP) immunoreactive (IR) neurons in the paraventricular nucleus (PVN), and the occurrence and distribution of nNOS spinally projecting neurons in the PVN of the female rat. Using double labelling immunohistochemistry, we mapped the distribution of nNOS-, OT- and AVP-immunoreactive (IR) neuronal cell bodies in the different parts of the PVN. About 80% of nNOS-IR cell bodies were magnocellular. About 30% of the nNOS-IR cell bodies were OT-IR, colocalization being most frequent in the rostral parts. In comparison, only approximately 3% of all nNOS-IR cell bodies were AVP-IR, evenly distributed throughout the PVN. True Blue (TB), administered unilaterally into the spinal cord, disclosed that most spinally projecting cell bodies in the PVN were localized in caudal parts. Combined TB tracing and nNOS immunohistochemistry showed that approximately 30% of spinally projecting neurons in the PVN were nNOS-IR, and that approximately 40% of these were magnocellular. Ipsilateral nNOS spinal projections were about eight times more frequent than the contralateral nNOS projections. The study describes the detailed neuroanatomical organization of nNOS neurons coexpressing OT or AVP, and of nNOS spinally projecting neurons within defined parts of the PVN. In contrast to the paraventriculo-spinal system in general, we show that the nNOS paraventriculo-spinal pathway to a large extent originates in magnocellular cell bodies. The results suggest that NO is an important messenger in the paraventriculo-spinal pathway that may in part act in concert with OT.
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PMID:Nitric oxide synthase in the hypothalamic paraventricular nucleus of the female rat; organization of spinal projections and coexistence with oxytocin or vasopressin. 1145 27

Despite considerable advances, both the central regulation of erection with processing of various stimuli, and the different steps involved in neurotransmission, impulse propagation and intracellular transduction of neural signals in penile smooth muscles, are still incompletely known. Centrally as well as peripherally, many transmitters and transmitter systems are involved. Dopamine, nitric oxide, 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 (eg noradrenaline, endothelins, angiotensins) and relaxant (eg NO, VIP and related peptides, prostanoids) factors controls the degree of contraction of the smooth muscle of the corpora cavernosa, and determines the functional state of the penis. Neurogenic NO is considered the most important factor for relaxation of penile vessels and corpus cavernosum. The roles of other putative transmitters/mediators and of various intracellular mechanisms, producing relaxation of vascular and corpus cavernosum smooth muscle, have not been established. For example, recent findings have suggested a role of Rho/Rho-kinase in the regulation of cavernosal tone, and that Rho-kinase antagonism could be a new potential principle for the treatment of erectile dysfunction. Further research in this area may be rewarding.
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PMID:Neurophysiology/pharmacology of erection. 1147 87

The effect of EP 91073, EP 51389, EP 70555 and EP 51216, peptide analogues of the growth hormone releasing peptide hexarelin, on penile erection induced by EP 80661 or EP 60761 injected into the paraventricular nucleus of the hypothalamus, was studied in male rats. Of the above peptides only EP 91073 (0.2-1 microg) was found capable of reducing penile erection induced by EP 80661 or EP 60761, when given into the paraventricular nucleus. Despite its ability to prevent EP peptide-induced penile erection, EP 91073 (1 microg) was unable to prevent penile erection induced by the dopamine receptor agonist apomorphine (50 ng), oxytocin (30 ng) and N-methyl-D-aspartic acid (50 ng), when given into the paraventricular nucleus 10 min prior to the above substances. The EP 91073-induced prevention of penile erection occurred with a reduction in the increase in nitric oxide production that occurs in the paraventricular nucleus concomitant to penile erection induced by EP 80661 and EP 60761, as measured by intracerebral vertical microdialysis. The present results are in line with the hypothesis that EP 80661 and EP 60761 induce penile erection by activating specific receptors in the paraventricular nucleus, located possibly in oxytocinergic neurons mediating penile erection, and show that EP 91073 acts as an antagonist of these EP peptide receptors mediating penile erection.
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PMID:EP 91073 prevents EP 80661-induced penile erection: new evidence for the existence of specific EP peptide receptors mediating penile erection. 1148 62

1. In myometrial strips from near-term non-labouring human uterus, addition of oxytocin (OT) evoked dose-dependent (10 - 3000 nM) phasic contractions that were antagonized by atosiban (1 microM) and relaxed by addition of the nitric oxide donor S-nitroso L-cysteine (Cys-NO). In near-term labouring myometrium, however, addition of OT was ineffective at raising additional tone. 2. In both labouring and non-labouring tissue, Cys-NO mediated relaxation of spontaneous or OT-induced contractions (IC(50)=1 microM) was unaffected by prior addition of the guanylyl cyclase (GC) inhibitors ODQ (1H-[1,2,4]oxadiazolo[4,3,-alpha]quinoxalin-1-one; 1 microM), or methylene blue (MB; 10 microM). 3. Elevation of intracellular cyclic GMP accompanying 30 microM Cys-NO addition in non-labouring tissue (7.5 fold) or in labouring tissues (2.5 fold) was completely blocked in tissues that had been pre-treated with ODQ or MB. 4. Charybdotoxin (ChTx), iberiotoxin (IbTx) and kaliotoxin (KalTx) all shifted the Cys-NO inhibition curve to the right and reduced the degree of relaxation produced by maximal Cys-NO treatment (100 microM in non-labouring tissue; in labouring tissue, KalTx prevented Cys-NO mediated relaxation in both stimulated and unstimulated tissue. 5. Addition of the NO-donor S-nitroso N-acetyl penicillamine (SNAP) produced a dose-dependent relaxation of pregnant myometrium while 3-morpholinosyndonimine (SIN-1) did not. The failure of SIN-1 to relax OT-induced contractions was not due to a failure of the donor to stimulate myometrial GC. 6. We demonstrate that despite the ability of NO to stimulate myometrial GC in pregnant uterine muscle, relaxations are independent of cyclic GMP action. Effects of K(+)-channel inhibitors suggests that NO-induced relaxation in human uterine smooth muscle may be subserved by direct or indirect activation of one or more calcium-activated K(+)-channels.
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PMID:NO-induced relaxation of labouring and non-labouring human myometrium is not mediated by cyclic GMP. 1152 13

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

The secretory peptides luteinizing hormone-releasing hormone, enkephalin, angiotensin, and oxytocin are biochemical antioxidants in aqueous medium. These hormones scavenge free peroxyl radicals, prevent the oxidation of low-density lipoprotein, and inhibit lipid peroxidation in brain membranes. Their capacity to directly suppress free radical-mediated reactions is demonstrated by electron-spin resonance spectroscopy. Electrospray ionization-mass spectrometry analysis of the free radical-quenching reaction reveals distinct oxidation products, including peptide dimers. Moreover, secretory peptide hormones can scavenge reactive nitrogen species derived from nitric oxide and peroxynitrite. An analysis of the structure-activity relationship indicates that their antioxidant activity is derived from the occurrence of solvent-exposed tyrosine and tryptophan residues, which is consistent with the mass spectrometry results. Significant effects in vitro can be observed at nanomolar concentrations, which makes these peptides comparable in potency with classic antioxidants having low molecular mass. Secretory peptide hormones may constitute an important part of the antioxidant defense system, and the sequences of the described antioxidant peptides may be unique lead structures for the rational design of novel antioxidant drugs having an improved pharmacological profile.
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PMID:Secretory peptide hormones are biochemical antioxidants: structure-activity relationship. 1180 49

This review will focus on the activity of oxytocin neurons in the supraoptic nucleus (SON) and some factors that regulate their function during parturition and milk ejection in the rat. The level of oxytocin increases in the blood during parturition following a regression of the corpus luteum. The increase in oxytocin secretion is presumably a consequence of releasing the oxytocin neurons from restraining inhibitory influences of endogenous opioids-, nitric oxide-, and GABA-containing neurons following declining blood levels of progesterone on the one hand and increasing levels of estrogen on the other during late pregnancy. However, the principal stimulus for the increased oxytocin release is believed to originate, at least in part, from mechanical stimulation to the uterine cervix by fetuses near term, the resultant uterine contractile activity, and the fetal expulsion reflex. Hence, the contractile activity of the uterus acts through positive feedback mechanisms during parturition to stimulate oxytocin neurons as well, and this further increases the secretion of oxytocin. During suckling in lactating rats, somatosensory stimuli from the pups induce intermittent synchronized burst firing of oxytocin neurons, resulting in pulsatile increases in blood oxytocin concentrations to cause milk ejection. The oxytocin neurons appear to have an intrinsic capability to fire in a bursting fashion as determined by observation of this phenomenon in brain slice or tissue culture preparations. The release of oxytocin within the microenvironment of the SON and paraventricular nucleus coupled with morphological reorganization in these nuclei play important roles in the bursting activity of each oxytocin neuron and synchronization in vivo. However, the mechanism responsible for the synchronization of electrical activity in oxytocin neurons in the four discrete hypothalamic nuclei remains an interesting unanswered question.
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PMID:Role of the supraoptic nucleus in regulation of parturition and milk ejection revisited. 1181 Jul 14

The magnocellular neurosecretory cells (MNCs) in the supraoptic nucleus (SON) express multiple kinds of genes, including not only the classical hormones arginine vasopressin (AVP) and oxytocin (OXT), but also other physiologically active substances including neuropeptides, their receptors, and nitric oxide (NO) synthase, the rate-limiting enzyme in the synthesis of NO under physiological condition. For example, osmotic stimuli such as dehydration and chronic salt loading cause a wide range of changes of the expression levels of the genes and marked induction of the expression of the genes in the SON. The expression of the NO synthase gene in the SON under physiological conditions is reviewed.
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PMID:Gene expression in the supraoptic nucleus. 1181 Jul 18

The increased expression of contraction-associated proteins, including oxytocin receptors, connexin-43, and prostaglandin F2alpha receptors, in term pregnant myometrium is classically considered to be the concrete expression of myometrial activation. However, the decrease in prostaglandin E2 receptor subtype EP2 on one hand and the down-regulation of the nitric oxide (NO) pathway and various vasorelaxing peptides on the other hand probably also play a key role in the loss of quiescence, and, with the above-mentioned activation, in the maturation of the myometrium. Decidual activation and production of interleukin-1, tumour necrosis factor-alpha and epidermal growth factor enhance prostaglandin production in both the amnion and chorion, and also in the myometrium. A substantial increase of eicosanoids concentration in myometrial tissue is probably an important condition for the success of the ultimate step of myometrial stimulation and the onset of labour. During labour, prostaglandins and oxytocin seem to act in synergy, perhaps along with endothelin-1, to trigger contractility through an increase in intracellular Ca2+ concentration. An overall view of these phenomena in which myometrial cells are the common targets of uterorelaxant and uterotonic agents appears essential for a rational use of tocolytic therapies and labour inductors.
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PMID:Myometrial maturation and labour. 1181 51

Our knowledge of the regulation of cerebral blood flow (CBF) in ectothermic vertebrates is still very limited. In endothermic vertebrates several peptides have been shown to affect CBF through nitric oxide (NO) dependent mechanisms. Using epi-illumination microscopy in rainbow trout in vivo, we have examined the effects of topically administered oxytocin, arginine vasopressin, substance P and bradykinin on the CBF (measured as erythrocyte velocity in venules on the optic lobes). Of these peptides, only oxytocin induced a dose dependent increase in CBF velocity. Blood pressure remained unchanged and the effect was suppressed by the NOS inhibitor, N(omega)-nitro-L-arginine. This indicates that oxytocin causes NO mediated vasodilation in rainbow trout brain.
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PMID:Oxytocin stimulates cerebral blood flow in rainbow trout (Oncorhynchus mykiss) through a nitric oxide dependent mechanism. 1185 26


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