The difference in the inhibitory mechanisms of papaverine on vascular and intestinal smooth muscles.
Papaverine (0.3-100 microM) more potently inhibited phenylephrine (1 microM)-induced contraction than 65 mM K+-induced contraction of the aorta, while it equally inhibited contractions induced by 65 mM K+ and carbachol (1 microM) in ileal smooth muscle. In phenylephrine-treated aorta, papaverine (1-10 microM) increased the cAMP and cGMP content. However, in carbachol-treated ileum, 30 microM papaverine partially increased the cAMP content while it maximally relaxed the preparation. In fura2-loaded aorta, papaverine (0.3-10 microM) inhibited both the contraction and the increase in intracellular Ca2+ level ([Ca2+]i) induced by phenylephrine in parallel. However, papaverine inhibited carbachol-induced contraction with only a small decrease in [Ca2+]i. Papaverine (1-30 microM) inhibited the carbachol-induced increase in oxidized flavoproteins, an indicator of increased mitochondrial oxidative phosphorylation, in ileal smooth muscle whereas it did not change the phenylephrine-induced increase in the aorta. These results suggest that papaverine inhibits smooth muscle contraction mainly by the accumulation of cAMP and/or cGMP due to the inhibition of phosphodiesterase in the aorta whereas, in ileal smooth muscle, papaverine inhibits smooth muscle contraction mainly by the inhibition of mitochondrial respiration.
Kaneda
T
T
Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Musashino, Tokyo, Japan.
Shimizu
K
K
Nakajyo
S
S
Urakawa
N
N
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005420:Flavoproteins / Q000378:metabolism; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010208:Papaverine / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D005420:Flavoproteins; D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D010208:Papaverine; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium