The difference in the inhibitory mechanisms of papaverine on vascular and intestinal smooth muscles

Papaverine (0.3–100 μM) more potently inhibited phenylephrine (1 μM)-induced contraction than 65 mM K +-induced contraction of the aorta, while it equally inhibited contractions induced by 65 mM K + and carbachol (1 μM) in ileal smooth muscle. In phenylephrine-treated aorta, papaverine (1–10 μM) inc...

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Bibliographic Details
Published in:European journal of pharmacology 1998-08, Vol.355 (2), p.149-157
Main Authors: Kaneda, Takeharu, Shimizu, Kazumasa, Nakajyo, Shinjiro, Urakawa, Norimoto
Format: Article
Language:English
Subjects:
Animals
Aorta
Aorta - drug effects
Aorta - physiology
Biological and medical sciences
Calcium - metabolism
Cardiovascular system
Cyclic AMP - metabolism
Cyclic GMP - metabolism
Cyclic nucleotide
Digestive system
Flavoproteins - metabolism
Ileum
Ileum - drug effects
Ileum - physiology
In Vitro Techniques
Male
Medical sciences
Mitochondria - drug effects
Muscle Contraction - drug effects
Muscle, Smooth - drug effects
Muscle, Smooth - physiology
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - physiology
Oxidative metabolism
Papaverine
Papaverine - pharmacology
Pharmacology. Drug treatments
Phosphodiesterase Inhibitors - pharmacology
Rats
Rats, Wistar
Vasodilator Agents - pharmacology
Vasodilator agents. Cerebral vasodilators
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Summary:Papaverine (0.3–100 μM) more potently inhibited phenylephrine (1 μM)-induced contraction than 65 mM K +-induced contraction of the aorta, while it equally inhibited contractions induced by 65 mM K + and carbachol (1 μM) in ileal smooth muscle. In phenylephrine-treated aorta, papaverine (1–10 μM) increased the cAMP and cGMP content. However, in carbachol-treated ileum, 30 μM papaverine partially increased the cAMP content while it maximally relaxed the preparation. In fura2-loaded aorta, papaverine (0.3–10 μM) inhibited both the contraction and the increase in intracellular Ca 2+ level ([Ca 2+] i) induced by phenylephrine in parallel. However, papaverine inhibited carbachol-induced contraction with only a small decrease in [Ca 2+] i. Papaverine (1–30 μM) 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.
ISSN:0014-2999
1879-0712
DOI:10.1016/S0014-2999(98)00479-8