Abstract

The effects of the β 2-adrenoceptor agonist formoterol (50 nM) on the angiotensin II (20 nM)-induced Ca 2+ response and changes in the cell volume and microviscosity of the plasma membrane of vascular smooth muscle cells were studied. Applied as a model substance for the stimulation of the phosphoinositide-phospholipase C pathway, angiotensin II has been used to simulate the bronchospasm of smooth muscle in asthma. Our results demonstrated that angiotensin II-induced smooth muscle contraction primarily involves an InsP 3-mediated release of Ca 2+ from intracellular stores and, to a minor extent, an enhanced influx of Ca 2+ through the plasma membrane. Both the Ca 2+ response and the contractile reaction were strongly antagonized by pretreatment of the cells with 50 nM formoterol. The protective effect of formoterol on smooth muscle contractions is proposed to be mainly related to a direct stimulation of β 2-adrenoceptor-coupled cAMP generation. Moreover, it is predicted that the interaction between the β 2-adrenoceptor glycoprotein and adenylate cyclase will be enhanced following a formoterol-associated decrease in the microviscosity of the plasma membrane.

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