Relaxation mechanisms of neferine on the rabbit corpus cavernosum tissue in vitro.
OBJECTIVE
To investigate the relaxation mechanisms of neferine (Nef) on the rabbit corpus cavernosum tissue in vitro.


METHODS
Strips of rabbit corpus cavernosum were mounted in organ chambers. The effects of Nef were examined on isolated muscle strips precontracted with phenylephrine (PE) alone, in the presence of N(W)-nitro-L-arginine (LNNA, a nitric oxide synthase inhibitor), 1-H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, a guanylyl cyclase inhibitor), indomethacin (cyclooxygenase inhibitor), tetraethylammonium (Ca(2+)-activated K(+) channel blocker), 4-aminopiridine (4-AP, voltage dependent K(+) channel blocker) and glibenclamide (ATP sensitive K(+) channel blocker). The effects of Nef on KCl-induced contraction of isolated muscle strips were also investigated. The procedure of calcium absence-calcium addition was designed to observe the effect of Nef on two components of the contractile responses to PE based on the source of Ca(2+) (extracellular vs. intracellular).


RESULTS
Corpus cavernosum strips relaxed in response to Nef (10(-9)-10(-4) mol/L) in a concentration-dependent manner with an IC(50) of 4.60 X 10(-6) mol/L. However, they were not affected by LNNA, ODQ, indomethacin or K(+)-channel blockers. Nef (10(-6) mol/L, 10(-5) mol/L) concentration dependently reduced the maximal contraction response of isolated strips induced by KCl to 79.3%+/-5.5% and 61.5%+/-3.2%, respectively (P < 0.01). In the calcium absence-calcium addition procedure, Nef 10(-5) mol/L inhibited both intracellular calcium-dependent and extracellular calcium-dependent contraction induced by PE (2 X 10(-5) mol/L) (P < 0.05). The inhibition ratios were 26.2%+/-5.4% and 48.3%+/-7.6%, respectively.


CONCLUSIONS
The results of the present study suggest that Nef possesses a relaxant effect on rabbit corpus cavernosum tissues, which is attributable to the inhibition of extracellular Ca2+ influx and the inhibition of release of intracellular stored Ca(2+), but not mediated by the release of nitric oxide, prostaglandins or by the activation of potassium channels.
Chen
Jun
J
Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China.
Qi
Jun
J
Chen
Fang
F
Liu
Ji-Hong
JH
Wang
Tao
T
Yang
Jun
J
Yin
Chun-Ping
CP
D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D010413:Penis / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; C057222:neferine; D011189:Potassium Chloride; D002118:Calcium