Effect of caffeine on tone and intracellular Ca++ release in guinea-pig and human trachealis.
High concentrations of methylxanthines induce contraction in many smooth muscle types, but relax guinea-pig trachealis. We examined this discrepancy by studying the interaction of caffeine and spasmogens in the isolated guinea-pig trachealis. We extended our observations to the isolated human trachealis. In the guinea-pig trachealis, 25 mM but not 2.5 mM caffeine totally blocked any contractile effect of methacholine or histamine, but not of KCl, whose contractile effect relies on extracellular Ca++. The beta-adrenergic agent isoprenaline (10(-3)M) only partially blocked the spasmodic effect of methacholine and histamine. In the human trachealis, 25 mM but not 2.5 mM caffeine induced an initial contraction followed by a relaxation. After this latter relaxation, methacholine (10(-5) M) and histamine (10(-5) M) were without effect, while KCl caused a contraction. In the guinea-pig, a contractile effect of 25 mM but not 2.5 mM caffeine was uncovered by switching to a high K+, Ca(++)-free solution prior to adding the caffeine. The source of the Ca++ promoting the contraction thus must be intracellular stores. Accordingly, ryanodine, an inhibitor of Ca++ storage, blocked this contraction. Similarly histamine (10(-5) M) and methacholine (10(-5) M) in the Ca(++)-free solution induced a contraction. The histamine contraction was completely blocked by ryanodine, the methacholine contraction, 79% blocked. We conclude that caffeine appears to surpass the antispasmodic effects of beta-adrenergic stimulation, at least in part, by depleting intracellular stores of Ca++.
Chideckel
E W
EW
Department of Medicine, West Virginia University, Morgantown 26506.
Anireddy
D R
DR
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D008688:Methacholine Compounds; D012433:Ryanodine; D002110:Caffeine; D011189:Potassium Chloride; D006632:Histamine; D007545:Isoproterenol; D002118:Calcium