Phorbol myristate acetate causes in guinea-pig lung parenchymal strip a maintained spasm which is relatively resistant to isoprenaline

• Published in: FEBS letters 1985-10, Vol.190 (1), p.6-10
• Main Authors: Dale, M.Maureen, Obianime, W.
• Format: Article
• Language: English
• Subjects: Aminophylline - pharmacology; Animals; Applied sciences; Asthma; Biological and medical sciences; Colforsin - pharmacology; DMSO, dimethyl sulphoxide; Exact sciences and technology; Guinea Pigs; Histamine - pharmacology; In Vitro Techniques; Isoproterenol - pharmacology; Lung - drug effects; Male; Medical sciences; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Nitroprusside - pharmacology; Other techniques and industries; Pharmacology. Drug treatments; Phorbol ester; Phorbols - pharmacology; PMA, phorbol myristate acetate; Polyphosphoinositide; Protein kinase; Respiratory system; Smooth muscle; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(85)80415-4

The effect of phorbol myristate acetate (PMA) was compared with that of histamine on the guinea-pig lung parenchymal strip. PMA, 10 −5 M, caused a slowly developing sustained contraction which had approximately the same magnitude as the maximal histamine contraction. Isoprenaline, at 10 −5 M, caused 86% relaxation of the histamine contraction but only 22% relaxation of the PMA contraction. Forskolin, at 10 −5 M had a similar action to isoprenaline on the effects of both spasmogens while aminophylline, 5 × 10 −4 M, was considerably less effective. Sodium nitroprusside had little effect on the histamine contraction and actually increased the PMA spasm. It is suggested that protein kinase C may have a role in the tonic phase of the contraction of bronchiolar smooth muscle. These findings could have relevance for the delayed phase of asthma, which is known to be insensitive to β-agonists.