Phasic responses to carbachol in isolated guinea pig trachea are augmented by cooling and inhibited by nifedipine.
Steady-state and kinetic approaches were used to study the effects of cooling to 25 degrees C and nifedipine (1 microM) on the phasic and tonic responses to 0.3 and 10 microM carbachol (Carb) in isolated segments of epithelium-free guinea pig trachea. Cooling and nifedipine had no effect on the steady-state tensions of the contractile responses to Carb in Krebs-bicarbonate buffer, but did inhibit the response to 40 mM KCl. Cooling increased the tensions of the phasic responses to both concentrations of Carb in Ca(++)-depleted, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-containing buffer, whereas the rate constant of decay of the phasic response (kdecay) was decreased only at 0.3 microM Carb. Nifedipine inhibited the tension and increased the kdecay of the phasic response to 10 microM Carb at both 37 and 25 degrees C. The phasic response to 0.3 microM Carb was essentially completely inhibited by nifedipine. The tension of the tonic response to Carb was unaffected by cooling and was only inhibited by nifedipine at 0.3 microM Carb at 37 degrees C. Both cooling and nifedipine, at 37 degrees C, decreased the rate constant of onset of the tonic response (kon) to Carb. The predominant effect of cooling to augment the phasic component of the contractile response to Carb, whereas it does not provide the mechanism to explain the enhanced bronchoconstrictor response of airways to cold, does suggest that Ca++ mobilization is altered by cold and that this may contribute to the enhanced bronchoconstrictor response.(ABSTRACT TRUNCATED AT 250 WORDS)
Tagliente
T M
TM
Department of Anesthesiology, Mt. Sinai School of Medicine of the City University of New York, New York.
Dalton
B A
BA
Ben-Harari
R R
RR
D000818:Animals; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003080:Cold Temperature; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects; D014132:Trachea / Q000187:drug effects
D011976:Receptors, Muscarinic; D011189:Potassium Chloride; D002217:Carbachol; D009543:Nifedipine