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)
Cortijo
J
J
Department of Farmacologia, Facultat de Medicina, Universitat de València, Spain.
Gonzalez
M
M
Ortiz
J L
JL
Morcillo
E
E
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D003080:Cold Temperature; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects; D014132:Trachea / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D010703:Phorbol Esters; C008874:phorbol-12,13-diacetate; D010042:Ouabain; D000584:Amiloride; D014700:Verapamil; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase