Nitric oxide-cyclic GMP signaling pathway in the regulation of rabbit clitoral cavernosum tone.
We investigated the role of nitric oxide (NO)-guanosine 3',5'-cyclic monophosphate (cGMP) signaling in the regulation of rabbit clitoral cavernosum (CC) tone. Tension measurements, reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and NADPH-diaphorase staining were performed in CC. In the precontracted CC strips with phenylephrine (10(-5) M), acetylcholine (ACh) relaxed, dependent on dosage. Pretreatment with atropine, N(omega) nitro-L-arginine-methyl ester (NAME) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), guanylate cyclase inhibitor abolished the ACh-induced relaxations, but tetrodotoxin (TTX) did not. Sodium nitroprusside relaxed the strips in the presence of atropine and NAME, but not in the presence of ODQ. Electrical field stimulation (EFS) relaxed the strips dependent on stimulus strength. Pretreatment with TTX, NAME, or ODQ abolished the EFS-induced relaxation, but atropine did not. L-Arginine partially restored the inhibited response to ACh and EFS. The inducible NO synthase (iNOS) and neuronal NOS (nNOS) mRNAs and iNOS and endothelial NOS (eNOS) proteins were identified in the CC. NADPH-diaphorase staining revealed the positivity on the nerve trunks and fine nerve fibers in the CC. Finally, results demonstrate that the nNOS, ENOS, and the NO-cGMP signaling pathway are involved in the regulation of clitoral tumescence.
Park
Jong Kwan
JK
Institute of Cardiovascular Research, Institute for Medical Sciences, Department of Urology, Medical School, Chonbuk National University, Chonju, 560-180, South Korea. rain@moak.chonbuk.ac.kr
Kim
Jung Ui
JU
Lee
Soon Oak
SO
Hwang
Pyoung Han
PH
Yi
Ho Keun
HK
Kim
Young Gon
YG
Cho
Kyung Woo
KW
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002987:Clitoris / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D017931:DNA Primers; D005260:Female; D066298:In Vitro Techniques; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
D017931:DNA Primers; D009569:Nitric Oxide; D009252:NADPH Dehydrogenase; D006152:Cyclic GMP; D000109:Acetylcholine