Inhibition of tracheal smooth muscle contraction and myosin phosphorylation by ryanodine.
Previous studies have shown that muscarinic activation of airway smooth muscle in low Ca++ solutions increases myosin phosphorylation without increasing tension. Blocking Ca++ influx reduced phosphorylation, but not to basal levels. It was proposed that release of intracellular Ca++ contributed to dissociation of phosphorylation and contraction. To test this hypothesis the effects of ryanodine were studied under similar conditions. Ryanodine (10(-7) to 10(-5) M) antagonized caffeine-induced contraction of canine tracheal smooth muscle. Ryanodine also reduced carbachol-induced contractions and carbachol-induced myosin phosphorylation. The effect of ryanodine on potassium and serotonin-induced contractions was also investigated to test for a nonspecific inhibitory effect. In contrast to the effect on carbachol responses, ryanodine (10(-5) M) potentiated the contractile response to low concentrations of serotonin and potassium, but had no effect on the maximum response to either stimulant. Carbachol (10(-6) M) and ryanodine (10(-5) M) both significantly decreased 45Ca++ content of tracheal muscle. The effect of ryanodine and carbachol together on 45Ca++ content was not greater than either drug alone suggesting that ryanodine reduces the caffeine and carbachol responses by depleting releaseable Ca++ stores. Ryanodine significantly reduced Ca++-induced contraction and myosin phosphorylation in carbachol-stimulated muscle, suggesting that some of the Ca++ responsible for elevated phosphorylation is released from the sarcoplasmic reticulum.
Gerthoffer
W T
WT
Department of Pharmacology, University of Nevada School of Medicine, Reno.
Murphey
K A
KA
Khoyi
M A
MA
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000037:antagonists & inhibitors; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D002217:Carbachol / Q000037:antagonists & inhibitors; D004285:Dogs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*; D010766:Phosphorylation; D012433:Ryanodine / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D000470:Alkaloids; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D012433:Ryanodine; D002110:Caffeine; D002217:Carbachol; D009218:Myosins; D002118:Calcium