Differential roles of ryanodine- and thapsigargin-sensitive intracellular CA2+ stores in excitation-contraction coupling in smooth muscle of guinea-pig taenia caeci.
1. To explore roles of intracellular Ca(2+) stores in excitation-contraction coupling in smooth muscle, we examined the effects of ryanodine, a fixer of ryanodine receptor-Ca(2+) channels to an open state, and thapsigargin, a selective inhibitor of the Ca(2+) pump in the intracellular stores, on smooth muscle contraction in the presence and absence of extracellular Ca(2+) in guinea-pig taenia caeci. 2. In Ca(2+) -free solution, contractions induced by 0.1 mmol/L carbachol and 0.1 mmol/L histamine were reduced to approximately 65% of control by either 1 micro mol/L thapsigargin or 10 micro mol/L ryanodine. In contrast, caffeine-induced contraction was reduced to approximately 40% of control by ryanodine, but was not affected by thapsigargin. 3. In the presence of extracellular Ca(2+), thapsigargin slowly induced a large and sustained contraction. In contrast, ryanodine did not induce an apparent contraction, but increased the sensitivity of contractile responses to receptor agonists (carbachol, AHR-602 and histamine) or depolarizing high K(+) with no changes in the maximal contraction. 4. These results suggest that there are pharmacological and physiological differences between ryanodine- and thapsigargin-sensitive intracellular Ca(2+) stores in excitation-contraction coupling in smooth muscle, which may be responsible for their differential effects on the Ca(2+) -influx pathway.
Hishinuma
Shigeru
S
Department of Pharmacodynamics, Meiji Pharmaceutical University, Tokyo, Japan. hishi@my-pharm.ac.jp
Saito
Masaki
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D002432:Cecum / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D011759:Pyrrolidines; D012433:Ryanodine; C004296:N-benzyl-3-pyrrolidylacetate methobromide; D019284:Thapsigargin; D006632:Histamine; D002217:Carbachol; D011188:Potassium; D002118:Calcium