Inhibitory mechanism of papaverine on carbachol-induced contraction in bovine trachea.
We have demonstrated that the relaxing mechanism of papaverine in phasic muscles such as ileum, urinary bladder, and uterus is different from tonic muscles such as aorta. In this study, we examined the inhibitory mechanism of papaverine on carbachol (CCh)-induced contraction in the bovine trachea. Papaverine inhibited muscle contraction and increase in [Ca(2+)](i) level induced by CCh. Papaverine increased cAMP content but not cGMP content. Papaverine did not affect CCh-induced oxidized flavoproteins fluorescence or reduced pyridine nucleotides fluorescence. Papaverine (30 microM) remarkably inhibited muscle tension, but slightly decreased creatine phosphate and ATP contents. Iberiotoxin restored the inhibitions of muscle contraction and [Ca(2+)](i) level induced by papaverine or dibutyryl-cAMP. These results suggested that the relaxing mechanism of papaverine in the bovine trachea is mainly due to increases of cAMP content by inhibiting phosphodiesterase and the mechanism is partially involved in the activation of BK channel by cAMP.
Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Tokyo, Japan. t-kaneda@nvau.ac.jp
Takeharu
T
Kaneda
Yukako
Y
Takeuchi
Hirozumi
H
Matsui
Kazumasa
K
Shimizu
Norimoto
N
Urakawa
Shinjiro
S
Nakajyo
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000037:antagonists & inhibitors*; D002417:Cattle; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D010208:Papaverine / Q000494:pharmacology*; D010725:Phosphocreatine / Q000032:analysis; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D010726:Phosphodiesterase Inhibitors; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D002217:Carbachol; D010208:Papaverine; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium