Agonist-mediated regulation of alpha 1- and beta 2-adrenergic receptors in cloned MDCK cells.
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.
Meier
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Sperling
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Insel
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D002999:Clone Cells; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D007668:Kidney; D007700:Kinetics; D008858:Microscopy, Phase-Contrast; D011458:Prostaglandins E / Q000378:metabolism; D011863:Radioimmunoassay; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D011458:Prostaglandins E; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D015232:Dinoprostone; D004837:Epinephrine