The relaxation mechanisms of tetrandrine on the rabbit corpus cavernosum tissue in vitro.
The relaxation mechanisms of tetrandrine (Tet) on the rabbit corpus cavernosum tissue in vitro were investigated. Strips of rabbit corpus cavernosum were mounted in organ chambers. The effects of Tet were examined on isolated muscle strips pre-contracted 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 (TEA, 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 Tet 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 Tet on the two components of the contractile responses to PE based on the source of Ca(2+) (extracellular vs. intracellular). Corpus cavernosum strips showed relaxation in response to Tet (10(-8) approximately 10(-3) mol L(-1)) in a concentration-dependent manner with an IC(50) of 3.73 x 10(-5) mol L(-1). However, they were not affected by LNNA, ODQ, indomethacin and K(+)-channel blockers. Tet (10 micromol L(-1), 30 micromol L(-1)) concentration dependently reduced the maximal contraction response of isolated strips induced by KCl to (73.0 +/- 3.8) and (41.5 +/- 3.4)%, respectively (p < 0.01). In the procedure of calcium absence-calcium addition, Tet 100 micromol L(-1) inhibited both intracellular calcium-dependent and extracellular calcium-dependent contraction induced by PE (20 micromol L(-1)) (p < 0.05). The inhibition ratios were (23.8 +/- 7.1) and (40.7 +/- 11.2)%, respectively. The results of the present study suggest that Tet possesses a relaxant effect on rabbit corpus cavernosum tissues, which is attributable to the inhibition of extracellular Ca(2+) 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, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Liu
Jihong
J
Wang
Tao
T
Xiao
Hengjun
H
Yin
Chunping
C
Yang
Jun
J
Chen
Xiaowen
X
Ye
Zhangqun
Z
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010413:Penis / Q000187:drug effects* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D031609:Stephania tetrandra / Q000737:chemistry; D019789:Tetraethylammonium / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D026902:Potassium Channel Blockers; D011810:Quinoxalines; D019335:Nitroarginine; C009438:tetrandrine; D019789:Tetraethylammonium; D011189:Potassium Chloride; D015761:4-Aminopyridine; D005905:Glyburide; D007213:Indomethacin