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

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 X 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 beta-agonists.