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Phorbol myristate acetate causes in guinea-pig lung parenchymal strip a maintained spasm which is relatively
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 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.
Insights
Phorbol myristate acetate (PMA) causes sustained lung smooth muscle contraction, unlike histamine. This PMA-induced contraction is resistant to beta-agonists, suggesting a role for protein kinase C in asthma.
Area of Science:
- Pharmacology
- Physiology
- Biochemistry
Background:
- Histamine is a known bronchoconstrictor.
- Asthma involves airway smooth muscle contraction, with delayed phases often unresponsive to beta-agonists.
Purpose of the Study:
- To compare the effects of phorbol myristate acetate (PMA) and histamine on guinea-pig lung parenchymal strips.
- To investigate the potential role of protein kinase C in airway smooth muscle contraction.
Main Methods:
- Guinea-pig lung parenchymal strips were used to assess smooth muscle contraction.
- The effects of PMA, histamine, isoprenaline, forskolin, aminophylline, and sodium nitroprusside were evaluated.
Main Results:
- PMA induced a sustained contraction comparable to maximal histamine contraction.
- Isoprenaline and forskolin showed significantly less relaxation on PMA-induced contraction compared to histamine-induced contraction.
- Aminophylline was less effective, and sodium nitroprusside increased PMA-induced spasm.
Conclusions:
- Protein kinase C activation may contribute to the tonic phase of airway smooth muscle contraction.
- These findings may explain the refractoriness of the delayed phase of asthma to beta-agonists.