Simultaneous measurement of Ca2+ transients and changes in the cell volume and microviscosity of the plasma membrane in smooth muscle cells. Evaluation of the effect of formoterol.
The effects of the beta 2-adrenoceptor agonist formoterol (50 nM) on the angiotensin II (20 nM)-induced Ca2+ 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 InsP3-mediated release of Ca2+ from intracellular stores and, to a minor extent, an enhanced influx of Ca2+ through the plasma membrane. Both the Ca2+ 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 beta 2-adrenoceptor-coupled cAMP generation. Moreover, it is predicted that the interaction between the beta 2-adrenoceptor glycoprotein and adenylate cyclase will be enhanced following a formoterol-associated decrease in the microviscosity of the plasma membrane.
Ochsner
M
M
Ciba-Geigy Ltd., Department of Physics, Basle, Switzerland.
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D000804:Angiotensin II; D002118:Calcium; D000068759:Formoterol Fumarate