Lysophosphatidic acid enhances contractility of isolated airway smooth muscle

The effects of the simple phospholipid mediator lysophosphatidic acid (LPA) on the contractile responsiveness of isolated tracheal rings from rabbits and cats were assessed. In both species, LPA increased the contractile response to the muscarinic agonist methacholine, but LPA did not induce contraction on its own. Conversely, LPA decreased the relaxation response to the beta-adrenergic-agonist isoproterenol in both species. Concentrations of LPA as low as 10(-8) M were effective, and the effects of LPA were rapidly reversed on washing. Phosphatidic acid was much less effective, requiring higher concentrations and producing only a minimal effect. Contractions induced by serotonin and by substance P also were enhanced by LPA, but KCl-induced contractions were unaffected. LPA inhibited the isoproterenol-induced relaxation of KCl-precontracted rings, similar to its effects on methacholine-precontracted rings, and relaxation induced by the direct adenylyl cyclase activator forskolin was inhibited in a manner similar to that induced by isoproterenol. Epithelium removal did not alter the contraction-enhancing effect of LPA. The ability of LPA to both enhance contraction and inhibit relaxation of airway smooth muscle suggests that LPA could contribute to airway hypercontractility in asthma, airway inflammation, or other types of lung injury.