Differential effects of N-formyl-methionyl-leucyl-phenylalanine and substance P on the electrical and contractile properties of airway smooth muscle cells.

Abstract

We have investigated the effect of substance P (SP) and N-formyl-methionyl-leucyl-phenylanine (f-Met-Leu-Phe) on airway smooth muscle preparations isolated from male guinea pigs. Alterations in both the resting membrane potential and developed isometric force were determined. Addition of SP (10(-10) to 10(-4) M) caused a nonphasic, dose-dependent, sustained depolarization of airway smooth muscle cells, with the concomitant development of increased isometric force. In contrast, f-Met-Leu-Phe (10(-12) to 10(-6) M) induced a biphasic membrane response of airway smooth muscle cells, i.e., a dose-dependent rapid depolarization, followed by prolonged hyperpolarization. During the depolarization phase, a significant transient increase in the isometric force was observed. A selective N-formyl peptide antagonist, t-boc-phenylalanyl-leucyl-phenylalanyl-leucyl-phenylalanine, prevented the f-Met-Leu-Phe-induced changes in membrane polarity and increase in isometric force, as did amiloride (10(-5) M), the selective sodium channel blocker. However, these agents had no effect on SP-induced changes in membrane potential or isometric force. These findings suggest that airway smooth muscle of guinea pigs possess both N-formyl peptide and SP receptors but that occupation of these receptors by their respective agonists leads to functionally distinct responses.