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Inhibitory effects of caffeine on contractions and calcium movement in vascular and intestinal smooth muscle
Author(s) -
Ahn H.Y.,
Karaki H.,
Urakawa N.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11430.x
Subject(s) - caffeine , contraction (grammar) , carbachol , endocrinology , medicine , chemistry , forskolin , muscle contraction , taenia coli , vascular smooth muscle , calcium , aorta , biology , smooth muscle , stimulation
1 The mechanism of the inhibitory effect of caffeine was investigated using vascular smooth muscle of rabbit aorta and intestinal smooth muscle of taenia isolated from guinea‐pig caecum. 2 Caffeine, 0.5–10 m m , relaxed the sustained contraction induced by 65.4 m m KCl or 10 −6 m noradrenaline in aorta, and by 45.4 m m KCl or 10 −6 m carbachol in taenia. The inhibitory effect of caffeine on the high K + ‐induced contraction was antagonized by external Ca 2+ but not by the Ca 2+ channel activators, Bay K 8644 (10 −7 m ) or CGP 28,392 (10 −7 m ). Forskolin (2 × 10 −7 m ) potentiated the inhibitory effect of caffeine on the noradrenaline‐induced contraction but not on the high K + ‐ or carbachol‐induced contraction. Caffeine induced a time‐and concentration‐dependent increase in the cyclic AMP content of aorta and forskolin caused a further augmentation. 3 45 Ca 2+ uptake was increased by high K + or noradrenaline in aorta and by high K + or carbachol in taenia. The increments were inhibited by caffeine at concentrations needed to inhibit muscle contractions. 4 45 Ca 2+ in the cellular releasable site in aorta was decreased either by noradrenaline or by caffeine. Simultaneous application of noradrenaline and caffeine did not induce an additive decrease. 5 In aorta treated with a Ca 2+ ‐free solution, caffeine induced only a small contraction. Noradrenaline induced a greater contraction which was inhibited by caffeine. After washout of caffeine and noradrenaline, the second application of noradrenaline induced a transient contraction suggesting that caffeine does not deplete the noradrenaline‐sensitive store. Caffeine did not inhibit Ca 2+ accumulation by the noradrenaline‐sensitive store. 6 It was concluded that caffeine has multiple sites of action in smooth muscle. Caffeine releases Ca 2+ from a store which is apparently not sensitive to noradrenaline. Caffeine may inhibit noradrenaline‐induced Ca 2+ release. Caffeine itself induces only a small contraction possibly because it decreases the Ca 2+ sensitivity of contractile filaments and/or increases Ca 2+ extrusion. Further, caffeine seems to inhibit stimulated Ca 2+ influx. Cyclic AMP may be only partly responsible for the inhibitory effect of caffeine.