Involvement of beta 3-adrenergic receptor activation via cyclic GMP- but not NO-dependent mechanisms in human corpus cavernosum function.
The beta(3)-adrenoreceptor plays a major role in lipolysis but the role and distribution of beta(3)-receptors in other specific sites have not been extensively studied. beta(3)-adrenergic receptors are present not only in adipose tissue but also in human gall bladder, colon, prostate, and skeletal muscle. Recently, beta(3)-adrenergic receptor stimulation was shown to elicit vasorelaxation of rat aorta through the NO-cGMP signal transduction pathway. Here we show that beta(3)-receptors are present in human corpus cavernosum and are localized mainly in smooth muscle cells. After activation by a selective beta(3)-adrenergic receptor agonist, BRL 37344, there was a cGMP-dependent but NO-independent vasorelaxation that was selectively blocked by a specific beta(3)-receptor antagonist. In addition, we report that the human corpus cavernosum exhibits basal beta(3)-receptor-mediated vasorelaxant tone and that beta(3)-receptor activity is linked to inhibition of the RhoA/Rho-kinase pathway. These observations indicate that beta(3)-receptors may play a physiological role in mediating penile erection and, therefore, could represent a therapeutic target for treatment of erectile dysfunction.
Cirino
Giuseppe
G
Dipartimento di Farmacologia Sperimentale, Facoltà di Medicina Università di Napoli-Federico II, 80131 Naples, Italy.
Sorrentino
Raffaella
R
di Villa Bianca
Roberta d'Emmanuele
Rd
Popolo
Ada
A
Palmieri
Alessandro
A
Imbimbo
Ciro
C
Fusco
Ferdinando
F
Longo
Nicola
N
Tajana
Gianfranco
G
Ignarro
Louis J
LJ
Mirone
Vincenzo
V
D015153:Blotting, Western; D006152:Cyclic GMP / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D010413:Penis / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*
D022702:Receptors, Adrenergic, beta-3; D009569:Nitric Oxide; D006152:Cyclic GMP