Neuromodulation of penile erection: an overview of the role of neurotransmitters and neuropeptides

Argiolas, Antonio; Melis, Maria Rosaria

doi:10.1016/0301-0082(95)80003-q

Cited by 126 publications

(97 citation statements)

References 174 publications

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“…Other putative proerectile neurotransmitters in the penis have not yet been compared. For example, besides acetylcholine, CGRP, VIP, and related peptides have been detected in the free nerve endings of the human corpus cavernosum and have been shown to be effective relaxants of human corpus cavernosum preparations and to increase cavernous arterial flow and smooth muscle relaxation when injected intercavernously in animals (1,35). In situ hybridization of glans tissue sections using the MC4R RNA probe identified two different sensory receptor types: an end bulb of Krause and Raffini nerve ending.…”

Section: Discussionmentioning

confidence: 99%

A role for the melanocortin 4 receptor in sexual function

Ploeg

Martin

Howard

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

284

207

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By using a combination of genetic, pharmacological, and anatomical approaches, we show that the melanocortin 4 receptor (MC4R), implicated in the control of food intake and energy expenditure, also modulates erectile function and sexual behavior. Evidence supporting this notion is based on several findings: (i) a highly selective nonpeptide MC4R agonist augments erectile activity initiated by electrical stimulation of the cavernous nerve in wild-type but not Mc4r-null mice; (ii) copulatory behavior is enhanced by administration of a selective MC4R agonist and is diminished in mice lacking Mc4r; (iii) reverse transcription (RT)-PCR and non-PCR based methods demonstrate MC4R expression in rat and human penis, and rat spinal cord, hypothalamus, brainstem, pelvic ganglion (major autonomic relay center to the penis), but not in rat primary corpus smooth muscle cavernosum cells; and (iv) in situ hybridization of glans tissue from the human and rat penis reveal MC4R expression in nerve fibers and mechanoreceptors in the glans of the penis. Collectively, these data implicate the MC4R in the modulation of penile erectile function and provide evidence that MC4R-mediated proerectile responses may be activated through neuronal circuitry in spinal cord erectile centers and somatosensory afferent nerve terminals of the penis. Our results provide a basis for the existence of MC4R-controlled neuronal pathways that control sexual function.O ur understanding of the physiology and anatomy of erectile function has advanced considerably in recent years (1-4). Penile erection is a highly coordinated reflex that is subject to modulation at many levels of the neuraxis. Relaxation of smooth muscle fibers of erectile tissue and concomitant dilatation of the arterial supply in the penis produce penile erection. Activation of neurons in the sacral spinal cord triggers activity in the pelvic nerve and, subsequently, the cavernous nerve, which can lead to the release of mediators of vasorelaxation, including nitric oxide. These mediators modulate cyclic nucleotide levels resulting in Ca 2ϩ sequestration and relaxation of smooth muscle fibers of the corpora cavernosa and corpus spongiosum in the shaft of the penis to produce arterial dilatation, engorgement of the penis with blood, and tumescence. Erections can be triggered either by peripheral (tactile) or by central (visual, olfactory, auditory, or imaginative cues) activation of somatic pathways and, as such, are influenced by tonic and phasic activity in the lumbosacral spinal cord and the brain.Five melanocortin heterotrimeric GTP-binding protein (G protein)-coupled receptors have been identified as expressed in different tissues (5, 6). The functional role of each of these five melanocortin receptors is being defined. Rodent and human genetic and pharmacological evidence indicates that activation of melanocortin 4 receptor (MC4R) results in a lean phenotype, whereas inactivation of the MC4R results in obesity (7-10). Recent studies have demonstrated that MTII, a cyclic analogue of ␣-mel...

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Section: Discussionmentioning

confidence: 99%

A role for the melanocortin 4 receptor in sexual function

Ploeg

Martin

Howard

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

284

207

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“…Of these, the best known are manipulation of the genitalia, erotic fantasies and sleeping in humans, retraction of the penile sheath in restrained rats, and drugs and/or neuropeptides in freely moving rats. Depending on the context in which penile erection occurs, different central and peripheral neural and/or humoral mechanisms are thought to participate in its regulation (see Dail, 1987;Lue & Tanagho, 1987;Ignarro, 1992;Marson & McKenna, 1992;Meisel & Sachs, 1994;Sachs, 1995;Argiolas & Melis, 1995;Andersson & Wagner, 1995;Hull et al, 1995;Liu et al, 1997). Among neurotransmitters and neuropeptides that are involved at a central level in the control of penile erection, the best known are dopamine, serotonin, excitatory amino acids, nitric oxide (NO), adrenocorticotrophin, oxytocin and opioid peptides.…”

Section: Introductionmentioning

confidence: 99%

“…They can facilitate or inhibit penile erection by acting in several brain areas, e.g. the medial preoptic area, the paraventricular nucleus of the hypothalamus (PVN), the hippocampus, the amygdala, the bed nucleus of the stria terminalis, the medulla oblongata and the spinal cord (for a review on the central control of penile erection see Meisel & Sachs, 1994;Argiolas & Melis, 1995;Andersson & Wagner, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…the hippocampus, the medulla oblongata and the spinal cord) play an important part in the control of penile erection. Accordingly, dopamine agonists, the excitatory amino acid N-methyl-D-aspartic acid (NMDA), and oxytocin itself stimulate these oxytocinergic neurons to facilitate this sexual response, while opiate drugs inhibit the activity of these neurons to prevent penile erection induced by the above compounds (for a review see Argiolas & Melis, 1995). The activation of NO synthase in the PVN apparently mediates the stimulation of the oxytocinergic neurons that control penile erection.…”

Section: Introductionmentioning

confidence: 99%

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Nitric oxide production is increased in the paraventricular nucleus of the hypothalamus of male rats during non-contact penile erections and copulation

Melis

Succu

Mauri

et al. 1998

European Journal of Neuroscience

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Male rats put in the presence of a receptive female rat that they can see, hear and smell, but cannot touch, show penile erection episodes. These non-contact erections occur concomitantly with an increase in nitric oxide production in the paraventricular nucleus of the hypothalamus, as detected by the increase in the NO2- and NO3- concentration in the paraventricular dialysate obtained from these males by in vivo microdialysis. NO2- concentration increased from 0.81+/-0.12 to 2.51+/-0.43 microM and that of NO3- from 4.50+/-0.73 to 8.31+/-2.3 microM. The NO2- increase was prevented by the nitric oxide synthase inhibitor NG-nitro-L-arginine methylester (20 microg) given unilaterally in the paraventricular nucleus, which also prevented non-contact erections. In contrast, the nitric oxide scavenger haemoglobin (20 microg) prevented the NO2- increase, but not non-contact erections; while the guanylate cyclase inhibitor methylene blue (20 microg) was ineffective on either response. NO2-and NO3- concentration was also increased in the paraventricular dialysate of male rats during in copula penile erections, that is, when sexual activity was allowed with the receptive females. As found with non-contact erections, NG-nitro-L-arginine methylester prevented NO2- increase and impaired copulatory behaviour; haemoglobin prevented NO2- increase only; and methylene blue was ineffective on either response. The present results confirm that nitric oxide is a physiological mediator of penile erection at the level of the paraventricular nucleus of the hypothalamus.

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“…Interestingly, hypothalamic nuclei in turn receive information directly from the genital regions (Marson & McKenna, 1994;Rajaofetra et al, 1992;Sachs, 1995;Steers, 2000). In addition, it has been shown that the PVN (paraventricular nucleus) is activated during copulation and orgasm (Komisaruk & Whipple, 2005); this could be related to its specific endocrine function since it produces oxytocin, vasopressin, enkephalins, and dopamine (Argiolas & Melis, 1995). In particular, oxytocin has been demonstrated to trigger activity in structures belonging to the reward system after sexual-or social-relevant stimuli (Gregory, Cheng, Rupp, Sengelaub, & Heiman, 2015;Groppe et al, 2013;Scheele, Plota, Stoffel-Wagner, Maier, & Hurlemann, 2016;Scheele et al, 2013).…”

Section: Hypothalamusmentioning

confidence: 99%

Neuroanatomy and function of human sexual behavior: A neglected or unknown issue?

et al. 2019

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IntroductionSexual desire, arousal, and orgasm are mediated by complex, yet still not fully understood, interactions of the somatic and autonomic nervous systems operating at the central and peripheral levels. Disruption of endocrine, neural, or vascular response, caused by aging, medical illness, neurological diseases, surgery, or drugs, can lead to sexual dysfunctions, thus significantly affecting patients' quality of life.PurposeThis narrative review aims at characterizing the involvement of the central nervous system in human sexual behavior.MethodsA literature search was conducted using PubMed in its entirety up to June 2018, analyzing the studies dealing with the neurobiological and neurophysiological basis of human sexuality.ResultsSexual behavior is regulated by both subcortical structures, such as the hypothalamus, brainstem, and spinal cord, and several cortical brain areas acting as an orchestra to finely adjust this primitive, complex, and versatile behavior. At the central level, dopaminergic and serotonergic systems appear to play a significant role in various factors of sexual response, although adrenergic, cholinergic, and other neuropeptide transmitter systems may contribute as well.ConclusionsProviding healthcare professionals with information concerning sexual behavior may overcome useless and sometimes dangerous barriers and improve patient management, since sexual well‐being is considered one of the most important aspects of one's quality of life.

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Neuromodulation of penile erection: an overview of the role of neurotransmitters and neuropeptides

Cited by 126 publications

References 174 publications

A role for the melanocortin 4 receptor in sexual function

A role for the melanocortin 4 receptor in sexual function

Nitric oxide production is increased in the paraventricular nucleus of the hypothalamus of male rats during non-contact penile erections and copulation

Neuroanatomy and function of human sexual behavior: A neglected or unknown issue?

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