alpha 1- and beta 2-adrenergic receptor expression in the Madin-Darby canine kidney epithelial cell line.

Abstract
The Madin-Darby canine kidney (MDCK) cell line, derived from distal tubule/collecting duct, expresses differentiated properties of renal tubule epithelium in culture. The expression of adrenergic receptors in MDCK was studied to examine the role of catecholamines in the regulation of renal function. Radioligand-binding studies demonstrated, on the basis of receptor affinities of subtype-selective adrenergic agonists and antagonists, that MDCK cells have both .alpha.1- and .beta.2-adrenergic receptors. To determine whether these receptor types were expressed by the same cell, a number of clonal MDCK cell lines were developed. The clonal lines had stable but unique morphologies reflecting heterogeneity in the parent cell line. Some clones expressed only .beta.2-adrenergic receptors and were nonmotile, whereas others expressed both .alpha.1- and .beta.2-receptors and demonstrated motility on the culture substrate at low cell densities. In one clone, .alpha.- and .beta.-receptor expression was stable for more than 50 passages. Catecholamine agonists increased phosphatidylinositol turnover by activating .alpha.-adrenergic receptors and cellular cAMP accumulation by activating .beta.-adrenergic receptors. Guanine nucleotide decreased the affinity of isoproterenol for the .beta.2-receptor but did not alter the affinity of epinephrine for the .alpha.1-receptor. Evidently, .alpha.1- and .beta.2-receptors can be expressed by a single renal tubular cell, and the 2 receptors behave as distinct entities in terms of cellular response and receptor regulation. Heterogeneity of adrenergic receptor expression in MDCK clones may reflect properties of different types of renal tubule cells.