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Am J Physiol Lung Cell Mol Physiol 266: L113-L124, 1994;
1040-0605/94 $5.00
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AJP - Lung Cellular and Molecular Physiology, Vol 266, Issue 2 113-L124, Copyright © 1994 by American Physiological Society

ARTICLES

ETA and ETB receptors on single smooth muscle cells cooperate in mediating guinea pig tracheal contraction

T. Inui, A. F. James, Y. Fujitani, M. Takimoto, T. Okada, T. Yamamura and Y. Urade
International Research Laboratories, Ciba-Geigy Japan, Takarazuka.

We investigated the distribution of endothelin A (ETA) and ETB receptors in single smooth muscle cells and their contribution to ET-induced contractions of guinea pig trachea. ETA and ETB receptors were detected in smooth muscle membranes (maximum binding capacities of 810 and 360 fmol/mg protein and dissociation constants of 38 and 5.1 pM for 125I-labeled ET-1 and 125I-ET-3, respectively) and visualized autoradiographically in primary cultured cells. ET-1 and ET-3 evoked concentration-dependent increases in intracellular Ca2+ concentration and smooth muscle tension. The half-maximally effective concentrations of ET-1 and ET-3 at inducing contractions were 1.9 and 2.7 nM, respectively. The Ca2+ responses showed tachyphylaxis to both ETs after stimulation with ET-1, but only to ET-3 after stimulation with ET-3. Consecutive applications of ET-3 and ET-1 (10 nM each) classified the cells into ETA dominant (approximately 30%) responding to only ET-1, ETB dominant (approximately 20%) responding to only ET-3, and ETA- and ETB-possessing (approximately 50%) cells responding to both. The ETA antagonist, 10 microM BQ-123, attenuated ET-1-induced contractions but did not affect the ET-3-induced contractions. The results indicate that both receptors coexist in a major population of smooth muscle cells and cooperate in mediating ET-1-induced contractions.


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