Yohimbine relaxes the human corpus cavernosum through a non-adrenergic mechanism involving the activation of K+ATP-dependent channels.
The mechanism by which yohimbine relaxes the human corpus cavernosum remains unclear. Using the human corpus cavernosum strips immersed in isometric baths containing Krebs-Henseleit solution, this study investigates the effect of yohimbine on the relaxation of the human corpus cavernosum through nitrergic pathways involving the activation of ATP-dependent potassium channels (K(ATP)). The maximal relaxation induced by yohimbine in the human corpus cavernosum strips pre-contracted with phenylephrine was 100+/-0% and only 30.5+/-5.0% when they were pre-contracted with 60-mM potassium (K(+)) solution. The maximal relaxation induced by yohimbine in phenylephrine pre-contracted tissues was significantly inhibited by tetrodotoxin, 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or 7-nitroindazole (43.6, 36.1 and 42.6%, respectively). Neither the combination charybdotoxin-apamin nor tetraethylammonium altered the response of the human corpora cavernosa strips to yohimbine. Nevertheless, glibenclamide decreased the maximum relaxant response to yohimbine by 29.8% (P<0.05; n=12). The results suggest that yohimbine relaxes the human corpus cavernosum by a non-adrenergic, non-cholinergic mechanism, probably activating the nitrergic-soluble guanylate cyclase (NO-sGc) pathway and K(ATP).
Freitas
F C
FC
Surgery Division Urology, Ceara Federal University, Fortaleza, Ceara, Brazil. fernando1327@unifor.br
Nascimento
N R F
NR
Cerqueira
J B G
JB
Morais
M E A
ME
Regadas
R P
RP
Gonzaga-Silva
L F
LF
D000293:Adolescent; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D001341:Autonomic Nervous System / Q000187:drug effects; D006152:Cyclic GMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D054086:KATP Channels / Q000819:agonists*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010413:Penis / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D015016:Yohimbine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D055815:Young Adult
D000317:Adrenergic alpha-Antagonists; D007004:Hypoglycemic Agents; D007191:Indazoles; D054086:KATP Channels; D020030:Nitric Oxide Donors; D015016:Yohimbine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D005905:Glyburide; C080122:7-nitroindazole