Thapsigargin does not affect phenylephrine-induced contractions in the anococcygeus muscle of rats.
1. The aims of the present study were to investigate the contribution of intracellular calcium and to evaluate the effect of the antagonists of the intracellular calcium stores, thapsigargin and [8-(Diethylamino)-octyl-3,4,5-trimethoxybenzoate, HC1] TMB-8, on phenylephrine-stimulated contractions of rat anococcygeus smooth muscle, using functional studies. 2. Phenylephrine induced concentration-related contractions in both 2.5 mM Ca2(+)-free EGTA media. 3. In Ca2(+)-free media phenylephrine stimulated successive contractions, and the contractile response was abolished only after approximately 26 stimulations. 4. In Ca2(+)-free media, after incubation with 10 microM TMB-8 for 30 min, phenylephrine induced concentration-response curves that shifted to the right. The EC50 values were not changed, and the maximum contractile response was reduced by 39.2 +/- 7.6% in relation to phenylephrine-stimulated responses in absence of TMB-8. 5. Thapsigargin (1 microM) did not alter phenylephrine-stimulated contractions in Ca2(+)-free media. 6. These results indicate that intracellular Ca2+ plays an important role on phenylephrine-stimulated contractions on rat anococcygeus muscle and that the phenylephrine-sensitive intracellular Ca2+ store is not sensitive to thapsigargin.
da Silva
C
C
Laboratory of Pharmacology, College of Pharmaceutical Sciences, University of Sao Paulo, Ribeirao Preto, Brazil.
Bendhack
L M
LM
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D010656:Phenylephrine; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium