title: The Rho-kinase inhibitor Y-27632 and the soluble guanylyl cyclase activator BAY41-2272 relax rabbit vaginal wall and clitoral corpus cavernosum.
abstract: The effects of Y-27632, a Rho-kinase inhibitor and BAY41-2272, a soluble guanylyl cyclase activator, on the tone and nitrergic responses of rabbit vaginal wall and clitoral corpus cavernosum were investigated. Y-27632 and BAY41-2272 (10 nM-10 micro M) elicited concentration-dependent relaxation of phenylephrine-induced tone in both tissues. IC(50) values of Y-27632 for vaginal and clitoral tissues were 370+/-30 nM, and 467+/-14 nM, respectively. BAY41-2272 had IC(50) values of 478+/-54 nM and 304+/-38 nM respectively. The effect of the Y-27632 on the tissue tone was not affected by an inhibitor of nitric oxide synthase (L-NAME; 500 micro M). However, L-NAME reduced the potency of BAY41-2272 in the clitoral corpus cavernosum but not in the vaginal wall. BAY41-2272 enhanced nitrergic relaxation responses only in the clitoral corpus cavernosum. Y-27632 had no effect on nitrergic relaxations in either tissue. These results demonstrate that Y-27632 and BAY41-2272 elicit relaxation of the rabbit vaginal wall and clitoral corpus cavernosum.
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, Gower Street, Cruciform Building, London WC1E 6BT. s.cellek@ucl.ac.uk
authors.forename: Selim
authors.initials: S
authors.lastname: Cellek
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D002987:Clitoris / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase; D014621:Vagina / Q000187:drug effects* / Q000201:enzymology; D054460:rho-Associated Kinases
chemical_list: C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011720:Pyrazoles; D011725:Pyridines; D018160:Receptors, Cytoplasmic and Nuclear; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase