Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 458, Issue 1-2, Pages 183-189Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-2999(02)02730-9
Keywords
YC-1; guanylate cyclase; nitric oxide (NO); apomorphine; penile erection; corpus cavernosum
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The aim of present study was to characterize the in vitro and in vivo pharmacological effects of YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1benzyl indazole), a soluble guanylate cyclase activator, on corpus cavernosal smooth muscle and penile erectile activity. YC-1 relaxed phenylephrine precontracted cavernosal smooth muscle (EC50=4.4 muM) and this effect was partially antagonized by 1H-[1,2,4]oxadiazole [4,3-a]quinoxalin-1-one (ODQ). ODQ is a selective soluble guanylate cyclase inhibitor that completely blocked the relaxation induced by sodium nitroprusside, suggesting that YC-1 binds to soluble guanylate cyclase at a different site from nitric oxide (NO). Both YC-1 and sodium nitroprusside, but not sildenafil (1-100 muM) caused concentration-dependent increases in cyclic GMP levels in cultured rabbit cavemosal smooth muscle cells and produced synergistic effects. Intraperitoneal administration of YC-1 (10 mumol/kg) evoked penile erection in rats with 70% incidence. More importantly, YC-1 was able to significantly augment the pro-erectile effects of a suboptimal dose of apomorphine. These results suggest that the soluble guanylate cyclase activator YC-1 increases cyclic GMP levels, leading to relaxation of cavemosal smooth muscle. These biochemical events may be related to the pro-erectile properties of YC-1 in vivo. (C) 2002 Elsevier Science B.V. All rights reserved.
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