AJP - Cell Physiology, Vol 249, Issue 1 69-C77, Copyright © 1985 by American Physiological Society

ARTICLES

Agonist-mediated regulation of alpha 1- and beta 2-adrenergic receptors in cloned MDCK cells

K. E. Meier, D. M. Sperling and P. A. Insel

Chronic exposure of cells to neurotransmitters and hormones can result in a decrease in receptor number (down-regulation). We asked whether two different types of receptors on the same cell that can both respond to a particular hormone are identically regulated. For this study we used MDCK-D-1, a cloned renal epithelial cell line that coexpresses alpha 1- and beta 2-adrenergic receptors, as a model system in which to examine the effects of an adrenergic agonist on the expression and function of these receptors. MDCK-D-1 cells retain differentiated features of renal tubular epithelium with respect to morphology and hormonal responsiveness. When MDCK-D-1 cells were incubated for 21 h with 100 microM epinephrine, alpha 1- and beta 2-receptor numbers decreased by 81 and 90%, respectively. The down-regulation of beta 2-receptors proceeded more rapidly than that of alpha 1-receptors. Down-regulated cells showed a greater than 80% loss of both alpha 1- and beta 2-adrenergic responses (alpha 1: stimulation of prostaglandin E2 release; beta 2: elevation of adenosine 3',5'-cyclic monophosphate levels). We conclude that in renal epithelial cells chronic exposure to a catecholamine agonist can result in a profound decrease in the number of alpha 1- and beta 2-receptors, this down-regulation is accompanied by a loss of adrenergic response, and the kinetics of receptor loss are different for alpha 1- and beta 2-receptors.

This article has been cited by other articles:

				M. Yang, R. Büscher, K. Taguchi, B. Grübbel, P. A. Insel, and M. C. Michel Protein Kinase C Does Not Mediate Phenylephrine-Induced Down-regulation of Madin-Darby Canine Kidney Cell Alpha-1B Adrenoceptors J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 36 - 43. [Abstract] [Full Text]