Effects of phorbol 12,13-diacetate and its influence on spasmogenic responses in normal and sensitized guinea-pig trachea.
We have studied the effects of phorbol 12,13-diacetate (PDA) and its influence on a variety of spasmogenic responses in trachea isolated from normal and sensitized guinea-pigs. Tracheal preparations were denuded of epithelium, treated with indomethacin (2.8 microM), and cooled to 20 degrees C. In these experimental conditions, tracheal strips contracted to PDA (0.1 nM-1 microM). Contractions to PDA (1 microM) were greater in sensitized tissues. In normal trachea, contractions to PDA (0.1 microM) were depressed by H-7, 1-(5-isoquinolinyl-sulphonyl)-2-methylpiperazine, (50 microM), amiloride (10 microM), verapamil (10 microM) and Ca(2+)-free exposure. Similar effects were obtained in sensitized trachea except that PDA-induced contraction was resistant to verapamil and Ca(2+)-free exposure. Cooling (20 degrees C) of normal trachea substantially depressed the response to CaCl2 (in K(+)-depolarized tissues), KCl, histamine and 5-hydroxytryptamine without affecting the spasm induced by acetylcholine. This inhibitory effect of cooling was not observed in sensitized trachea. PDA (0.1 microM) did not affect spasmogenic responses at 37 degrees C but counteracted the inhibitory effect of cooling in normal trachea. PDA had no effect on sensitized tissues. PDA (0.1-1 microM) did not alter Ca(2+)-induced contraction of skinned normal and sensitized trachea. These results support the hypothesis that intracellularly stored Ca2+ plays an important role in the activation of sensitized tracheal muscle.
De Diego
A
A
Department de Farmacologia, Facultat de Medicina i Odontología, Universitat de València, Spain.
Cortijo
J
J
Villagrasa
V
V
Perpiñá
M
M
Esplugues
J
J
Morcillo
E J
EJ
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004232:Diuretics / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010703:Phorbol Esters / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D004232:Diuretics; D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D014665:Vasodilator Agents; C008874:phorbol-12,13-diacetate; D012701:Serotonin; D011189:Potassium Chloride; D000584:Amiloride; D006632:Histamine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D014700:Verapamil; D011493:Protein Kinase C; D002118:Calcium; D007213:Indomethacin