The effect of smooth muscle relaxants working through different transduction mechanisms on the phorbol dibutyrate-induced contraction of the guinea-pig lung parenchymal strip: possible relevance for asthma

Pulmonary Pharmacology
A W ObianimeM M Dale

Abstract

It has been suggested that protein kinase C activation may have a role in the maintained, 'latch-bridge' phase of smooth muscle contraction. We have examined the effects of a range of smooth muscle relaxants on the maintained contraction produced in the guinea-pig parenchymal lung strip by the protein kinase C activator, 4 beta-phorbol dibutyrate (4 beta-PDBu). The maximum histamine contraction (produced by 10 microM) was used as a standard and the effects of the smooth muscle relaxants were also studied on this histamine-induced contraction. After 4 beta-PDBu, 1 microM, had produced contraction, enprofylline, forskolin and papaverine caused concentration-dependent relaxation, producing total reversal of the contraction, while prostaglandin E2 and prostacyclin caused a concentration-dependent relaxation but less than total reversal. The concentrations required for the effects on the phorbol ester contraction were 10 to 100-fold higher than were necessary for relaxation of the maximum contraction produced by histamine. Isoprenaline, 1 microM, a concentration which caused total reversal of the histamine-induced contraction, caused only 22% decrease of the phorbol dibutyrate-induced contraction and no further relaxation occurred w...Continue Reading

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Citations

Dec 15, 1994·European Journal of Pharmacology·J E NallyJ C McGrath
Jul 6, 2000·European Journal of Pharmacology·B SarriáE J Morcillo
Dec 26, 2001·Toxicology and Applied Pharmacology·K Svens, A Ryrfeldt

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