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  • Title: Effects of phorbol 12,13-diacetate and its influence on spasmogenic responses in normal and sensitized guinea-pig trachea.
    Author: De Diego A, Cortijo J, Villagrasa V, Perpiñá M, Esplugues J, Morcillo EJ.
    Journal: J Pharm Pharmacol; 1995 Sep; 47(9):750-6. PubMed ID: 8583388.
    Abstract:
    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.
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