Calcitonin gene-related peptide: Possibly neurotransmitter contributes to penile erection in monkeys

doi:10.1016/0090-4295(93)90608-D

Urology

Volume 41, Issue 4, April 1993, Pages 397-401

https://doi.org/10.1016/0090-4295(93)90608-D Get rights and content

Abstract

The distribution of calcitonin gene-related peptide (CGRP) immunoreactivity in the cavernous tissue and the erectile response to intracavernous injection of CGRP was investigated in 7 monkeys. Intracavernous CGRP increased cavernous arterial flow and induced cavernous smooth muscle relaxation and venous outflow occlusion. Intracavernous injection of CGRP antibody did not significantly change the erectile response to cavernous nerve stimulation. Histologic staining for CGRP immunoreactivity showed nerve fiber-like staining within the cavernous arterial wall and the cavernous smooth muscles. These data suggest that CGRP may contribute to penile erection monkeys.

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Cited by (25)

Intracavernous delivery of synthetic angiopoietin-1 protein as a novel therapeutic strategy for erectile dysfunction in the type II diabetic db/db mouse
2010, Journal of Sexual Medicine
Citation Excerpt :
The cAMP second-messenger system does play a role in mediating penile erection and has been exploited in the management of ED. Several prostaglandins [43], vasoactive intestinal polypeptide [44], and calcitonin gene-related peptide [45] have been known to initiate cAMP-mediated smooth muscle relaxation in the penis. However, the effect of Ang1 on cAMP expression remains unclear.
Patients with erectile dysfunction (ED) associated with type II diabetes often have impaired endothelial function and tend to respond poorly to oral phosphodiesterase type 5 inhibitors. Therefore, neovascularization is a promising strategy for curing diabetic ED.
To determine the effectiveness of a soluble, stable, and potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, in promoting cavernous angiogenesis and erectile function in a mouse model of type II diabetic ED.
Sixteen-week-old male db/db mice (in which obesity and type II diabetes are caused by a mutation in the leptin receptor) and control C57BL/6J mice were used and divided into four groups (N = 14 per group): age-matched controls; db/db mice receiving two successive intracavernous injections of phosphate-buffered saline (PBS) (days −3 and 0; 20 µL); db/db mice receiving a single intracavernous injection of COMP-Ang1 protein (day 0; 5.8 µg/20 µL); and db/db mice receiving two successive intracavernous injections of COMP-Ang1 protein (days −3 and 0; 5.8 µg/20 µL).
Two weeks later, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was then harvested and stained with antibodies to platelet/endothelial cell adhesion molecule-1 (PECAM-1) (endothelial cell marker), phosphohistone H3 (PH3, a nuclear protein indicative of cell proliferation), phospho-endothelial nitric oxide synthase (eNOS), and eNOS. Penis specimens from a separate group of animals were used for cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) quantification.
Local delivery of COMP-Ang1 protein significantly increased eNOS phosphorylation and cGMP and cAMP expression compared with that in the group treated with PBS. Repeated intracavernous injections of COMP-Ang1 protein completely restored erectile function and cavernous endothelial content through enhanced cavernous neoangiogenesis as evaluated by PECAM-1 and PH3 immunohistochemistry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay, whereas a single injection of COMP-Ang1 protein elicited partial improvement.
Cavernous neovascularization using recombinant Ang1 protein is a novel therapeutic strategy for the treatment of ED resulting from type II diabetes. Jin H-R, Kim WJ, Song JS, Piao S, Tumurbaatar M, Shin SH, Choi MJ, Tuvshintur B, Song K-M, Kwon M-H, Yin GN, Koh GY, Ryu J-K, and Suh J-K. Intracavernous delivery of synthetic angiopoietin-1 protein as a novel therapeutic strategy for erectile dysfunction in the type II diabetic db/db mouse.
Neuropeptides in the rat corpus cavernosum and seminal vesicle: Effects of age and two types of diabetes
2009, Autonomic Neuroscience: Basic and Clinical
To observe the development of neuropathic changes in two types of experimental diabetes using changes in concentrations of NPY, CGRP and amines in the corpora cavernosa and seminal vesicles. Type I diabetes was studied in Wistar rats after 12 and 16 weeks of STZ-induced hyperglycaemia, and Type II diabetes was studied in prediabetic GK rats aged 52 weeks. Both were compared with age-matched normal Wistar rats.
NPY and CGRP were estimated using radioimmunoassay, and amines using HPLC.
There were significant changes in [CGRP] in the normal corpus cavernosum and in [NPY] in the normal seminal vesicle with age.
STZ-diabetes, induced at 10 weeks of age, resulted in significant elevation of [NPY] and [CGRP] in the corpora cavernosa and seminal vesicles after 12 and 16 weeks of hyperglycaemia, relative to age-matched control rats.
The GK rats were intolerant of glucose at 52 weeks of age, but did not have raised fasting blood glucose levels. [NPY], [CGRP] and [noradrenaline] in corpora cavernosa were significantly increased in the prediabetic GK animals relative to age-matched Wistar control rats. The seminal vesicles of GK rats showed a significant increase in [NPY], a non-significant increase in [CGRP], and a fall in [noradrenaline] relative to the age-matched Wistar controls.
The results indicate increased levels of NPY and noradrenaline in autonomic nerves, and of CGRP in sensory nerves, innervating the corpus cavernosum in Type I and in prediabetic Type II GK rats.
Nitric oxide-mediated erectile effects of galantide but not galanin in vivo
2000, Nitric Oxide - Biology and Chemistry
The purpose of this study was to investigate the in vivo effects of intracavernosal injections of galanin and galantide (a specific galanin receptor antagonist) on penile erection in the anesthetized cat. Erectile responses to galanin and galantide were compared with responses to a standard triple drug combination [1.65 mg papaverine, 25 μg phentolamine, and 0.5 μg prostaglandin E₁ (PGE₁)]. Intracavernosal injections of galanin (3–100 nmol) and galantide (0.1–3 nmol) induced penile erection in a dose-dependent manner. In terms of relative potency, galantide was approximately 100-fold more potent than galanin at increasing cavernosal pressure. The maximal increases in intracavernosal pressure in response to galanin and galantide were 83 and 95%, respectively, of the control triple drug combination. The total durations of erectile response caused by these peptides were significantly shorter (P < 0.05) than those by the triple drug combination. The nitric oxide synthase inhibitor L-NAME (20 mg) significantly decreased the erectile response in the cat to galantide but not to galanin, while the K⁺_ATP channel antagonist U-37883A (3 mg) had no effect on the erectile response to galanin nor galantide. The results of the present study demonstrate that galantide, a putative antagonist for the galanin receptor, has more potent agonist activity than galanin in increasing intracavernosal pressure in the cat. Moreover, these data suggest that galantide, but not galanin, causes penile erection by an NO/cGMP-dependent mechanism. This is the first study to demonstrate that galanin may play a role in the physiology of penile erection.
Adrenomedullin induces penile erection in the cat
1997, European Journal of Pharmacology
The present study was undertaken to investigate the effects of intracavernosal injections of adrenomedullin, a novel hypotensive peptide, on penile erection in anesthetized cats. Responses to adrenomedullin were compared to those elicited by intracavernosal injection of the control triple-drug combination (1.65 mg papaverine, 25 μg phentolamine, and 0.5 μg prostaglandin E₁). Intracavernosal injections of adrenomedullin in doses of 0.1–1.0 nmol elicited dose-related increases in cavernosal pressure and penile length. The maximal effect of adrenomedullin injection on cavernosal pressure was an 8-fold increase in pressure, which was 74% of that induced by the triple-drug combination. The maximal effect on penile length was a 43% increase when compared to baseline value, which was comparable to that induced by the triple-drug combination. The duration of the peak pressure and total duration of the peptide effect were significantly shorter in response to the 1 nmol dose of adrenomedullin than was observed with the control triple-drug combination. Intracavernous injection of the control triple-drug combination resulted in a significantly greater decrease in systemic arterial blood pressure than did adrenomedullin. Erectile responses to adrenomedullin were not altered following administration of the nitric oxide synthase inhibitor, N^ω-nitro-l-arginine, at a time when erectile responses to acetylcholine were significantly reduced. These data demonstrate that intracavernous injection of adrenomedullin induces a short-lived erection in cats that is not due to the release of nitric oxide.
Could erectile dysfunction be a side effect of CGRP inhibition? A case report
2022, Cephalalgia
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Calcitonin gene-related peptide: Possibly neurotransmitter contributes to penile erection in monkeys

Abstract

J Urol

J Urol

Peptides

Eur J Pharmacol

Peptides

J Urol

Untersuchungen über die Erektion des Hundes

Beitr Anat Physiol

Neurohumoral transmission and the autonomic nervous system

Zur Physiologie den gefasserweiternden and gefässverengenden Nerven

St. Petersburg med Wchnscher

On the mechanism of erection

Am J Physiol

Hemodynamic mechanisms of erection in the canine penis

Am J Physiol

Neurophysiology of erection

Autonomic control of penile erection in the dog

J Physiol

The effect of atropine and alpha and beta blockers on human penile erection: a controlled pilot study