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Mechanisms controlling caffeine‐induced relaxation of coronary artery of the pig
Author(s) -
Bent Vincent,
Bény JeanLouis
Publication year - 1991
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.1476-5381.1991.tb12345.x
Subject(s) - caffeine , chemistry , contraction (grammar) , depolarization , acetylcholine , egta , muscle contraction , extracellular , biophysics , medicine , hyperpolarization (physics) , endocrinology , muscle relaxation , membrane potential , calcium , biochemistry , biology , stereochemistry , nuclear magnetic resonance spectroscopy , organic chemistry
1 We studied the effects of caffeine on coronary artery smooth muscle of the pig by measuring changes in isometric tension, cytosolic free Ca 2+ concentration ([Ca 2+ ] i ) and transmembrane potential. 2 In the absence of tone, caffeine induced a concentration‐dependent transient contraction of coronary artery strips, followed by sustained relaxation. Simultaneously with the relaxation, caffeine, 25 m m , hyperpolarized the smooth muscle cells by 7.7 ± 0.9 mV. 3 Caffeine caused a concentration‐dependent relaxation of strips precontracted with 10 −5 m acetylcholine (ACh). A supramaximal relaxing concentration of 25 m m caffeine produced an additional transient increase in [Ca 2+ ] i on the Ca 2+ plateau of ACh tonic contraction, which was followed by a decrease in [Ca 2+ ] i to a level slightly below the basal concentration. This relaxation was accompanied by a hyperpolarization of 7.3 ± 0.9 mV. 4 KCl 120 m m (high K + ) contracted the strips with a concomitant depolarization of 38.6 ± 1.6 mV and sustained increase in [Ca 2+ ] i . Caffeine caused a concentration‐dependent relaxation of high K + ‐induced contraction. Caffeine, 25 m m , decreased the Ca 2+ plateau to a level that remained above the basal concentration of Ca 2+ but did not change the membrane potential. 5 When strips were placed in a Ca 2+ ‐free medium with EGTA 2 m m and, in addition, ACh was applied successively three times, both intracellular and extracellular mobilizable Ca 2+ pools were depleted. In these conditions, phorbol 12,13 dibutyrate (PDBu) 10 −7 m and prostaglandin F 2α (PGF 2α ) 10 −5 m contracted the strips. Caffeine (25 m m ) inhibited these contractions with no change in [Ca 2+ ] i . 6 Forskolin, 3 × 10 −7 m , inhibited ACh induced‐contraction but did not affect those induced by PDBu. 7 In conclusion, these results show that caffeine has multiple cellular effects. During caffeine‐induced relaxation, [Ca 2+ ] i , adenosine 3′: 5′‐cyclic monophosphate (cyclic AMP) content and membrane potential are modified. The findings suggest, however, that these effects are secondary, and that caffeine acts mainly by another unknown mechanism, possibly involving a direct inhibition of the contractile apparatus.