Pharmacological studies into cyclo‐oxygenase, lipoxygenase and phospholipase in smooth muscle contraction in the isolated trachea

Abstract

1 Indomethacin (1 tM) enhanced histamine-induced contractions in pig and guinea-pig isolated tracheae. Mepacrine (30-50 pLM) abolished this effect of indomethacin suggesting that contractile metabolites of arachidonate are involved in the response to indomethacin. 2 Mepacrine (100 jM) in the absence of indomethacin also markedly reduced histamine-induced contractions (81.2% inhibition) in the pig trachea, without affecting responses to acetylcholine. Histamine-induced responses in the guinea-pig trachea were similarly reduced, but with a higher concentration of mepacrine (300 jiM). 3 BW755c (226 jM) enhanced histamine-induced contractions in some pig tracheal preparations and caused inhibition in others. These effects of BW755c were negatively correlated to the initial reactivity of the muscle to histamine such that weak contractions were potentiated and strong contractions were inhibited. A similar effect was seen with phenidone (100 jM). 4 The results with BW755c and phenidone suggest that muscle reactivity (to histamine) may be partly determined by the balance between the release of inhibitory and contractile arachidonate metabolites. Mepacrine exerts a different effect indicating that histamine-induced contractions are regulated by a mepacrine-sensitive process which appears to be separate from the metabolism of arachidonate.

Calcium ions and respiratory smooth muscle function.

“…), a chain of events is initiated that end up as the phenomena of smooth muscle contraction or relaxation but which may be greatly modified by the products of, for example, phospholipid metabolism (Figure 4). Some of these pathways may be involved in calcium gating mechanisms, and in addition may generate products of the arachidonic acid cycle which themselves modify the smooth muscle response (Mitchell, 1984). If the biochemical events themselves are not directly involved in calcium gating, entry or mobilisation of calcium by other mechanisms can switch on these processes, and these processes (the products of arachidonic acid metabolism) then go on to modify the smooth muscle response.…”