THE DIFFERENCE IN THE INHIBITORY MECHANISMS OF PAPAVERINE ON VASCULARAND INTESTINAL SMOOTH MUSCLES

Papaverine (0.3-100 mu M) more potently inhibited phenylephrine (1 mu M)-induced contraction than 65 mM K+-induced contraction of the aorta, while it equally inhibited contractions induced by 65 mM K+ and carba chol (1 mu M) in ileal smooth muscle. In phenylephrine-treated aorta, papaverine (1-10 mu M) increased the cAMP and cGMP content. However, i n carbachol-treated ileum, 30 mu M papaverine partially increased the cAMP content while it maximally relaxed the preparation. In fura2-load ed aorta, papaverine (0.3-10 mu M) inhibited both the contraction and the increase in intracellular Ca2+ level ([Ca2+](i)) induced by phenyl ephrine in parallel. However, papaverine inhibited carbachol-induced c ontraction with only a small decrease in [Ca2+](i). Papaverine (1-30 m u M) inhibited the carbachol-induced increase in oxidized flavoprotein s, an indicator of increased mitochondrial oxidative phosphorylation, in ileal smooth muscle whereas it did not change the phenylephrine-ind uced increase in the aorta. These results suggest that papaverine inhi bits smooth muscle contraction mainly by the accumulation of cAMP and/ or cGMP due to the inhibition of phosphodiesterase in the aorta wherea s, in ileal smooth muscle, papaverine inhibits smooth muscle contracti on mainly by the inhibition of mitochondrial respiration. (C) 1998 Els evier Science B.V. All rights reserved.