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PMID: 11399661 Published · ppublish English Journal Article

Y-27632, an inhibitor of Rho-kinase, antagonizes noradrenergic contractions in the rabbit and human penile corpus cavernosum.

British journal of pharmacology ·Vol. 133 ·No. 4 ·2001-06-00 ·Pages 455-8

Rees RW, Ralph DJ, Royle M, Moncada S, Cellek S

Abstract

We have examined the effect of an inhibitor of Rho-kinase, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632), on the contractions elicited by noradrenergic nerve stimulation and by phenylephrine in the human and rabbit penile corpus cavernosum. In both tissues, after treatment with scopolamine (10 microM) and N(G)-nitro-L-arginine methyl ester (L-NAME; 300 microM), electrical field stimulation (EFS) elicited noradrenergic contractions. These contractions were inhibited by Y-27632 in a concentration-dependent manner. The compound caused concentration-dependent relaxation of phenylephrine-contracted tissues, which were treated with scopolamine (10 microM), guanethidine (10 microM) and L-NAME (300 microM). These results suggest that Rho-kinase is involved in noradrenergic contractile pathway in the cavernosal smooth muscle of the penis.

MeSH Terms
Amides/pharmacology Animals Drug Interactions Electric Stimulation Enzyme Inhibitors/pharmacology Humans In Vitro Techniques Intracellular Signaling Peptides and Proteins Male Muscle Contraction/drug effects Muscle Relaxants, Central/pharmacology NG-Nitroarginine Methyl Ester/pharmacology Penis/drug effects,physiology Phenylephrine/pharmacology Protein Serine-Threonine Kinases/antagonists & inhibitors Pyridines/pharmacology Rabbits Synaptic Transmission/drug effects,physiology Vasoconstrictor Agents/pharmacology rho-Associated Kinases
Chemicals
Amides Enzyme Inhibitors Intracellular Signaling Peptides and Proteins Muscle Relaxants, Central Pyridines Vasoconstrictor Agents Y 27632 Phenylephrine Protein Serine-Threonine Kinases rho-Associated Kinases NG-Nitroarginine Methyl Ester
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Rees R W
The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6AE.
Ralph D J
Royle M
Moncada S
Cellek S
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
Published
2001-06-00
Pages
455-8
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1572821
Subset
IM
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