Effects of low temperature and pharmacological interventions on the responses of the isolated guinea-pig trachea.

Cooling the guinea-pig isolated trachea from 37 degrees C to 20 degrees C virtually abolished the response to CaCl2 (in K(+)-depolarized tissues) and depressed that to histamine (about 75% reduction), KCl and 5-hydroxytryptamine (around 50% inhibition) while the response to acetylcholine remained unaffected. A further cooling to 10 degrees C was necessary to inhibit acetylcholine-induced contractions. Hyporesponsiveness to spasmogens by cooling was not associated with subsensitivity (increased EC50) except for 5-hydroxytryptamine. Contractile responses to KCl (50 mmol/l), histamine (1 mmol/l) and 5-hydroxytryptamine (0.1 mmol/l) in a Ca(2+)-free EGTA (0.1 mmol/l)-containing solution were inhibited by cooling to 20 degrees C but responses to acetylcholine (1 mmol/l) in the same experimental conditions were not affected. Cooling to 20 degrees C after treatment with an antagonist (ouabain 10 mumol/l, amiloride 0.1 mmol/l or vanadate 0.1 mmol/l) or after incubation in K(+)-free medium or low Na+ (25 mmol/l) solution produced the same or greater inhibitions of tracheal responses to spasmogens than cooling alone. The guinea-pig trachea treated with phorbol 12,13-diacetate (PDA; 1 mumol/l) and cooled to 20 degrees C responded to spasmogens similarly to a trachea untreated with PDA at 37 degrees C. In contrast, PDA (1 mumol/l) did not counteract the depressed responsiveness to histamine of ouabain (10 mumol/l)- or amiloride (0.1 mmol/l)- treated tracheal strips at 37 degrees C. PDA (1 mumol/l) enhanced tracheal contractions caused by KCl (50 mmol/l) in Ca(2+)-free medium at 20 degrees C but failed to augment those to histamine in the same conditions.(ABSTRACT TRUNCATED AT 250 WORDS)