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

Abstract

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.