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Caffeine acting on pregnant rat myometrium: analysis of its relaxant action and its failure to release Ca 2+ from intracellular stores
Author(s) -
Savineau JeanPierre,
Mironneau Jean
Publication year - 1990
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.1476-5381.1990.tb14691.x
Subject(s) - caffeine , myometrium , chemistry , contraction (grammar) , oxytocin , endocrinology , medicine , uterine contraction , muscle contraction , sodium , calcium , stimulation , uterus , organic chemistry
1 The effect of caffeine on mechanical activity was studied in pregnant rat myometrium. 2 In muscle cells with intact plasmalemmae, caffeine (0.1–50 m m ) produced no contraction whatever the experimental conditions. 3 Caffeine (0.1–10 m m ) inhibited, in a concentration‐dependent manner, contractions induced by electrical stimulation, potassium‐rich (60 m m K + ) solution, sodium‐free solution or oxytocin (22.5 n m ). 4 In Ca 2+ ‐free solution, various substances (oxytocin, sodium orthovanadate and prostaglandin E 2 ) evoked sustained contractions that were suppressed by caffeine (5–10 m m ). When caffeine (> 5 m m ) was applied during Ca 2+ ‐loading of the tissue (2.1 m m Ca 2+ , 5 min) in the presence of a K + ‐rich solution, the subsequent transient contraction induced by a short application (10 s) of oxytocin (22.5 n m ) in Ca‐free solution was reduced (63 ± 3.5% reduction for 20 m m caffeine, n = 4). 5 In saponin‐skinned strips, application of caffeine (5–10 m m ) during loading of the Ca 2+ ‐store increased the subsequent contraction induced by myo‐inositol 1,4,5 trisphosphate (IP 3 , 10 μ m ). Caffeine (10–30 m m ) decreased calcium‐activated contractions in skinned fibres lacking a functional internal Ca‐store. This effect was reduced by the cyclic AMP‐dependent protein kinase inhibitor Thr‐Thr‐Tyr‐Ala‐Asp‐Phe‐Ile‐Ala‐Ser‐Gly‐Arg‐Thr‐Gly‐Arg‐Arg‐Asn‐Ala‐Ile‐His‐Asp (8 μ m ). 6 In conclusion, it is suggested that the inability of caffeine to cause spasm of rat myometrium is due to the absence of a caffeine‐sensitive calcium‐release channel in the sarcoplasmic reticulum. Relaxant effects of caffeine can be explained by mechanisms leading to a decrease in both the cytoplasmic free Ca 2+ concentration and the Ca 2+ ‐sensitivity of the contractile machinery.