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 peripheral pharmacology of local mechanisms of penile erection is known today thanks to recent advance in the study of the regulation of erectile tissue smooth muscle tone. Smooth muscle fibers present in the corpus cavernosum and arteries destined to the penis relax in response to the release of non adrenergic non cholinergic neuromediators synthetized by postganglionic parasympathetic nerve fibers present in the cavernous nerves. Nitric oxide is the main proerectile neuromediator. Noradrenaline, released by sympathetic fibers, contracts penile smooth muscle fibers and is antierectile. Recent progress in the peripheral pharmacology of penile erection allows new perspectives in the treatment of erectile dysfunction. The spinal cord represents a major site for the neural regulation of penile erection. The latter occurs in response to stimuli from peripheral or supraspinal origin. Different neural structures in the brainstem (nucleus paragigantocellularis), pons and hypothalamus (nucleus paraventricularis) send projections to the thoracolumbar sympathetic and lumbosacral parasympathetic nuclei at the origin of proerectile peripheral pathways. Serotonin and oxytocin are candidates as neuromediators involved in the supraspinal control of penile erection. Studying the central command of penile erection allows an approach to the pathophysiology of psychogenic erectile dysfunction.
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PMID:[Physiology of erection]. 918 54

Penile erections were regularly induced by intermittent subcutaneous injections of apomorphine in five patients with Parkinson's disease (PD) complicated by motor fluctuations. Four of the patients reported erectile dysfunction before beginning apomorphine and two of these report a significant improvement in their sexual function resulting from apomorphine use. Animal studies suggest central D2-type dopamine receptor stimulation and oxytocin release from the paraventricular nucleus of the hypothalamus mediate the effect. Erections reported with other dopamine agonists and levodopa are probably mediated by the same mechanism. Apomorphine-induced erections in PD are probably more common than previously thought. The benefit of apomorphine on sexual function in some patients suggests a possible role in the treatment of impotence in PD.
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PMID:Apomorphine-induced penile erections in Parkinson's disease. 1043 14

Central nervous system processes are fundamental to sexual function. Considerable progress has been made in our understanding of the neuroanatomical and neuropharmacological bases for erection. Based largely on rat models, there is adequate understanding presently of the general anatomical areas of the brain that relate to sexual function, including the medial amygdala, medial preoptic area, paraventricular nucleus, the periaqueductal gray, ventral tegmentum and others. There is also a burgeoning body of evidence implicating nitric oxide, dopamine, serotonin and oxytocin as critical central neurotransmitters involved in various aspects of sexual function. The role of dopamine, in particular, appears fundamental in the mediation of erectile responses in both animals and man. Additionally, clinical research with apomorphine, a D1/D2 agonist, has shown significant promise in improving erections in men with a wide range of erectile difficulties. Finally, a new classification matrix has been proposed for existing treatments for erectile dysfunction based upon the putative site and mechanism of action. Implications for the further development of neuropharmacological agents in this area are discussed.
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PMID:Central neuropharmacological agents and mechanisms in erectile dysfunction: the role of dopamine. 1088 Aug 21

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

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

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

A group of oxytocinergic neurons originating in the paraventricular nucleus of the hypothalamus and projecting to extrahypothalamic brain areas (e.g. hippocampus, medulla oblongata and spinal cord) control penile erection. Activation of these neurons by dopamine and dopamine agonists, excitatory amino acids (N-methyl-D-aspartic acid) or oxytocin itself, or by electrical stimulation leads to penile erection, while their inhibition by GABA and GABA agonists or by opioid peptides and opiate-like drugs inhibits this sexual response. The activation of oxytocinergic neurons in the paraventricular nucleus by dopamine, oxytocin and excitatory amino acids is apparently secondary to the activation of nitric oxide (NO) synthase. NO in turn activates, by a mechanism that is as yet unidentified, the release of oxytocin from oxytocinergic neurons in extrahypothalamic brain areas. Several peptide analogues of hexarelin, a growth hormone releasing peptide, also induce penile erection when injected into the paraventricular nucleus and, to a lesser extent, systemically, apparently by acting on a specific receptor to activate oxytocinergic neurons as shown for the above drugs and oxytocin. Paraventricular oxytocinergic neurons and mechanisms similar to those reported above are also involved in the expression of penile erection in physiological contexts, namely when penile erection is induced in the male by the presence of an inaccessible receptive female, which is considered a model for psychogenic impotence in man, as well as during copulation. These findings show that paraventricular oxytocinergic neurons projecting to extra-hypothalamic brain areas and to the spinal cord are a likely target for the treatment of erectile dysfunction of central origin.
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PMID:Central oxytocinergic neurotransmission: a drug target for the therapy of psychogenic erectile dysfunction. 1252 90

It is well established that transmitters of the nonadrenergic-noncholinergic (NANC) system are involved in the control of sexual arousal and penile erection in healthy males. The proerectile activity of dopamine D1/D2 receptor agonist apomorphine-HCl (IXENSE, UPRIMA) involves oxytocinergic pathways descending from the hypothalamus to the brain stem and spinal autonomic centers. Although it has been demonstrated that injection of oxytocin into the paraventricular nucleus and the hippocampus produces penile erection in rats, the significance of the peptide in the control of sexual arousal and penile erection in man has been, up until now, only poorly evaluated. The present study was undertaken to determine whether oxytocin (OT) plasma levels alter in the systemic and cavernous blood of healthy males under different penile conditions (flaccidity, tumescence, rigidity, detumescence). Twenty-five healthy adult males were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and rigid erection. Blood was taken from the corpus cavernosum (CC) and the cubital vein (CV) during penile flaccidity, tumescence, rigidity and detumescence. Following extraction from plasma aliqouts, oxytocin was measured by means of a radioimmunoassay. An increase was observed in the mean OT plasma levels in the systemic and cavernous blood when the flaccid penis became tumescent (CC: from 66.7+/-34 to 75+/-44 pg/ml; CV: from 71+/-41 to 79+/-49.5 pg/ml). From tumescence to rigidity, OT further rose in the cavernous blood (to 81+/-58 pg/ml), whereas it remained unaltered in the systemic circulation. During detumescence, oxytocin plasma levels dropped in the cavernous but again increased in the systemic blood (to 94+/-49 pg/ml). Our results support the hypothesis of a pivotal role of OT in the mechanism of male sexual arousal and penile erection and provide a rationale for the use of apomorphine in the treatment of erectile dysfunction.
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PMID:Oxytocin plasma levels in the systemic and cavernous blood of healthy males during different penile conditions. 1281 90

Apomorphine is a dopamine receptor agonist that was recently licensed for the treatment of erectile dysfunction. However, although sexual activity can be stressful, there has been little investigation into whether treatments for erectile dysfunction affect stress responses. We have examined whether a single dose of apomorphine, sufficient to produce penile erections (50 microg/kg, i.a.), can alter basal or stress-induced plasma ACTH levels, or activity of central pathways thought to control the hypothalamic-pituitary-adrenal axis in rats. An immune challenge (interleukin-1 beta, 1 microg/kg, i.a.) was used as a physical stressor while sound stress (100 dB white noise, 30 min) was used as a psychological stressor. Intravascular administration of apomorphine had no effect on basal ACTH levels but did substantially increase the number of Fos-positive amygdala and nucleus tractus solitarius catecholamine cells. Administration of apomorphine prior to immune challenge augmented the normal ACTH response to this stressor at 90 min and there was a corresponding increase in the number of Fos-positive paraventricular nucleus corticotropin-releasing factor cells, paraventricular nucleus oxytocin cells and nucleus tractus solitarius catecholamine cells. However, apomorphine treatment did not alter ACTH or Fos responses to sound stress. These data suggest that erection-inducing levels of apomorphine interfere with hypothalamic-pituitary-adrenal axis inhibitory feedback mechanisms in response to a physical stressor, but have no effect on the response to a psychological stressor. Consequently, it is likely that apomorphine acts on a hypothalamic-pituitary-adrenal axis control pathway that is unique to physical stressors. A candidate for this site of action is the nucleus tractus solitarius catecholamine cell population and, in particular, A2 noradrenergic neurons.
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PMID:Systemic apomorphine alters HPA axis responses to interleukin-1 beta administration but not sound stress. 1281 60

Activation of sacral parasympathetic pathways elicits penile erection through the release of vasorelaxant neurotransmitters that increase blood flow to the penis and relax the penile erectile tissue. Sympathetic pathways are antierectile. The pudendal pathway, responsible for the contraction of the perineal striated muscles, enhances an already present erection. All pathways originate in the spinal cord, but at various levels and areas. The convergence of information from peripheral and supra-spinal origins onto spinal neurones is very likely activating more specifically the spinal pro-erectile network. Peripheral information is the afferent limb of reflexive erections, impinges onto spinal interneurones and is able to activate or regulate the activity of sympathetic, parasympathetic and somatic nuclei. Supra-spinal information impinges onto either the same or a different spinal network. Premotor neurones located in supra-spinal structures, that project directly onto spinal sympathetic, parasympathetic or pudendal motoneurones, are present in the medulla, pons and diencephalon. Several of these premotor neurones may in turn be activated by sensory information from the genitals. Descending pathways release a variety of aminergic and peptidergic neurotransmitters in the vicinity of spinal neurones, thereby exerting complex effects on the spinal pro-erectile network. Brainstem and hypothalamic nuclei (among the latter, the paraventricular nucleus and the medial preoptic area) may not reach directly the spinal pro-erectile network. They are prone to regulate penile erection in more integrated and coordinated responses of the body, as those occurring during sexual behaviour. The pro-erectile central and spinal effects of neuropeptides such as oxytocin, melanocortins and endorphins have only recently been analyzed. Such compounds may represent therapeutic strategies to treat erectile dysfunction through a central site of action.
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PMID:[Neural control of erection]. 1566 38


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