Regional differences in the mechanical properties of rabbit airway smooth muscle

Abstract

1. In studies of rabbit airway smooth muscle, differences in mechanical responses to acetylcholine, histamine and high K+ in intact muscles, and in Ca2+ sensitivity in skinned muscles, have been examined in tissue taken from 5 different regions of the airway. Interactions between prostaglandin F2 alpha and epithio-thromboxane A2 and the above spasmogenic agencies were also studied. 2. Mechanical responses to histamine (10 microM) and to 128 mM K+ were smallest in trachea and were largest in 3rd and 4th order bronchi. In all regions, spasm evoked by 10 microM acetylcholine was greater than that evoked by 10 microM histamine or 128 mM K+. 3. In the third and fourth branches of the rabbit right middle bronchus, contractions evoked by 10 microM acetylcholine, 10 microM histamine and 128 mM K+ showed similar amplitudes of phasic response. In Ca2+-free solution containing 2 mM EGTA, the phasic components of the acetylcholine- or histamine-induced contraction remained unchanged in comparison with that observed in Krebs solution, but the phasic and tonic components of the K+-induced contraction and the tonic changes induced by acetylcholine and histamine were abolished. 4. Two subtypes of the histamine receptor, excitatory H1- and inhibitory H2- receptors were detected on the bronchial smooth muscle. The H1-induced contraction was mediated by release of stored Ca2+ together with activation of Ca2+ influx relatively insensitive to Ca2+ antagonists. 5. The -log(EC50) values for acetylcholine and histamine (in the presence of cimetidine and atropine) were 6.11 +/- 0.11 and 5.33 +/- 0.08, respectively, in the third branch of right middle bronchus. These values were similar to those observed for trachea. 6. Prostaglandin F2. (10 microM) and 9,11-epithio-11,12-methano-thromboxane A2 (0.1 microM) neither provoked nor enhanced the contractions evoked by any stimulants. 7. No difference was observed between the Ca2+ sensitivity of chemically skinned muscle from the trachea and that of muscle from the third branch of the right middle bronchus. 8. Regional differences in the response to histamine and acetylcholine observed in airway smooth muscles are discussed and it is concluded that these may be due to differences in receptor numbers.