Role of lysophosphatidylcholine in the desensitization of beta-adrenergic receptors by Ca2+ sensitization in tracheal smooth muscle

Lysophosphatidylcholine (Lyso-PC) is generally considered to promote tissue inflammation. To determine the involvement of exogenous Lyso-PC in the bet a -adrenergic desensitization by phospholipase A(2), we examined the inhibi tory effects of isoproterenol (ISO) on tension and intracellular Ca2+ conce ntration by methacholine (MCh) after continuous exposure to Lyso-PC in guin ea-pig tracheal smooth muscle, using isometric tension recordings and fura- 2 signal (F340/F380 ratio). Preexposure to 10 muM Lyso-PC markedly reduced subsequent inhibition by 0.3 muM ISO against I muM MCh-induced contraction in a time-dependent manner. in contrast, values of percent F340/F380 ratio for MCh with ISO were not affected after exposure to Lyso-PC. In the presen ce of Y-27632, a selective rhokinase inhibitor, a reduction in subsequent r elaxation by ISO after exposure to Lyso-PC was inhibited in a concentration -dependent manner. Preincubation with cholera toxin also inhibited reduced responsiveness to ISO by Lyso-PC. Pre-exposure to Lyso-PC did not attenuate subsequent relaxation by agents that bypass beta -adrenergic receptors. Th ese results indicate that continuous exposure to Lyso-PC may cause homologo us desensitization of beta -adrenergic receptors via an augmentation in sen sitivity to Ca2+ by rho, a small G protein, in airway smooth muscle, and th at activation of the stimulatory G protein of adenylyl cyclase, G(s), may p revent this phenomenon.