Epithelium-dependent regulation of smooth muscle contractility of the airways

Abstract

The contribution of calmodulin and protein kinase C to the regulation of epithelial relaxing factor production by the tracheal epithelium and the role of adenylate and guanylate cyclase in the realization of the effect of this factor on airway smooth muscles are studied by the mechanographic method with cascade perfusion. Calmodulin and protein kinase C are shown to participate in the production of relaxing factor by epitheliocytes, guanylate cyclase being the principal target in exposure of smooth muscles to epithelial relaxing factor. Key Words: epithelium; trachea; smooth muscles; contractionRecent studies have confirmed the capacity of airway epithelium to modulate the contractile reactions of smooth muscles [4,8,10]. By analogy with the function of vascular epithelium, the mechanism of the modulating effect may be related to the production of epithelial relaxing factor (ERF). Available data permit a general description of the mechanism of epithelial regulation of the contractility of vascular smooth muscles [3], but this concept evidently cannot be extrapolated to the epithelial-smooth muscle relationships in the airways. Specifically, the mechanisms of calcium-dependent regulation of ERF production are unknown. The type and role of interactions between the adenylate and guanylate cyclase signal systems in the course of epithelium-induced bronchial dilatation also require elucidation.In this research we studied the contribution of calmodulin (CM) and protein kinase C to the regulation of ERF production by tracheal epithelium and the role of adenylate and guanylate cyclase in the realization of the effect of ERF on the muscles of the airways.Siberian Medical University, Tomsk MATERIALS AND METHODSRing segments 3-4 mm wide and a 30-ram-long tubular preparation were cut from the trachea of outbred male white rats. The segment intended as the "acceptor" was mechanically deepithelialized as described previously [5]. The preparations were placed in a device for cascade perfusion [3]. Aerated Krebs' solution was delivered to the ERF "aeceptor" at a rate of 0.5 ml/min through the lumen of the tracheal tubular preparation (ERF "donor"). The mechanical tension of the "acceptor" was measured using a 6MX2B mechanotron under conditions approaching isometric.Calcium ionophore (A23187, 0.5 ~tM), added to Krebs' solution perfused through the "donor" lumen, initiated the production of ERF. The effects of ERF on the "acceptor" were assessed as the percent share of mechanical tension reduction in response to perfusion of hyperpotassium (30 mM) Krebs' solution. Krebs' solution of the following composition (mM) was used in the study: 120.4 NaC1, 5.9 KC1, 1.2 MgC12, 2.5 CaCI~, 1.2 NaH2PO4, 15.5 NaHCO3, and 11.5 glucose, pH 7.35 at 37~The test solutions were based on

Specific features of epithelium-dependent contractile reactions of smooth muscles in various subdivisions of the respiratory tract

“…There is ample evidence that respiratory epithelium participates in the control of smooth muscle (SM) contractile activity in the airways [4,6,10]. The state and functional activity of the epithelium strongly influences the contractile responses of SM-segments to catecholamines, cholinomimetic agents, histamine, and other physiologically active substances [5,8,11].…”