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.
MeSH Terms
Amides/pharmacology
Animals
Clitoris/drug effects,enzymology
Dose-Response Relationship, Drug
Enzyme Activation/drug effects,physiology
Enzyme Inhibitors/pharmacology
Female
Guanylate Cyclase
In Vitro Techniques
Intracellular Signaling Peptides and Proteins
Muscle Relaxation/drug effects,physiology
Protein Serine-Threonine Kinases/antagonists & inhibitors,metabolism
Pyrazoles/pharmacology
Pyridines/pharmacology
Rabbits
Receptors, Cytoplasmic and Nuclear/metabolism
Soluble Guanylyl Cyclase
Vagina/drug effects,enzymology
rho-Associated Kinases
Chemicals
3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine
Amides
Enzyme Inhibitors
Intracellular Signaling Peptides and Proteins
Pyrazoles
Pyridines
Receptors, Cytoplasmic and Nuclear
Y 27632
Protein Serine-Threonine Kinases
rho-Associated Kinases
Guanylate Cyclase
Soluble Guanylyl Cyclase
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Cellek Selim
Wolfson Institute for Biomedical Research, University College London, Gower Street, Cruciform Building, London WC1E 6BT. s.cellek@ucl.ac.uk
References (15)
15 references, click to expand
-
Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II.
J Physiol. 2000 Jan 15;522 Pt 2:177-85
PMID: 10639096
-
Release of nitric oxide from endothelial cells stimulated by YC-1, an activator of soluble guanylyl cyclase.
Br J Pharmacol. 1999 Nov;128(6):1316-22
PMID: 10578147
-
Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway.
Nat Med. 2001 Jan;7(1):119-22
PMID: 11135626
-
NO-independent regulatory site on soluble guanylate cyclase.
Nature. 2001 Mar 8;410(6825):212-5
PMID: 11242081
-
Y-27632, an inhibitor of Rho-kinase, antagonizes noradrenergic contractions in the rabbit and human penile corpus cavernosum.
Br J Pharmacol. 2001 Jun;133(4):455-8
PMID: 11399661
-
Effects of diabetes on neurotransmission in rat vaginal smooth muscle.
Int J Impot Res. 2001 Apr;13(2):58-66
PMID: 11426340
-
Characterization of the non-nitrergic NANC relaxation responses in the rabbit vaginal wall.
Br J Pharmacol. 2002 Jan;135(2):546-54
PMID: 11815390
-
Nitric oxide independent activation of guanylate cyclase by YC-1 causes erectile responses in the rat.
J Urol. 2002 May;167(5):2276-81
PMID: 11956492
-
RhoA-mediated Ca2+ sensitization in erectile function.
J Biol Chem. 2002 Aug 23;277(34):30614-21
PMID: 12060659
-
BAY41-2272, a novel nitric oxide independent soluble guanylate cyclase activator, relaxes human and rabbit corpus cavernosum in vitro.
J Urol. 2003 Feb;169(2):761-6
PMID: 12544359
-
Effect of YC-1, an NO-independent, superoxide-sensitive stimulator of soluble guanylyl cyclase, on smooth muscle responsiveness to nitrovasodilators.
Br J Pharmacol. 1997 Feb;120(4):681-9
PMID: 9051308
-
Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension.
Nature. 1997 Oct 30;389(6654):990-4
PMID: 9353125
-
YC-1 potentiates nitric oxide- and carbon monoxide-induced cyclic GMP effects in human platelets.
Mol Pharmacol. 1998 Dec;54(6):962-7
PMID: 9855623
-
Nitrergic neurotransmission mediates the non-adrenergic non-cholinergic responses in the clitoral corpus cavernosum of the rabbit.
Br J Pharmacol. 1998 Dec;125(8):1627-9
PMID: 9886752
-
Female sexual arousal disorder: new insights.
Int J Impot Res. 2000 Oct;12 Suppl 4:S152-7
PMID: 11035405