Beta-Adrenergic Receptors and Isoproterenol-stimulated Potassium Transport in Erythrocytes from Normal and Hypothyroid Turkeys

Abstract

A B S T R A C T We have previously reported that in hypothyroid turkeys the number of beta-adrenergic receptors in intact erythrocytes is reduced by -50% without any changes in the affinity of the receptor for the agonist, isoproterenol. In view of the physiological action of the catecholamines to stimulate bidirectional ion fluxes in these cells, we have now examined the possibility that the decrease in beta receptor number might be associated with concomitant changes in catecholamine-dependent potassium ion transport. Hypothyroid turkey erythrocytes display decreased sensitivity to isoproterenol-stimulated potassium influx.Half-maximal stimulation of potassium influx occurs at 9.2±+1.7 nM in hypothyroid cells as opposed to only 3.8±+0.4 nM in normal cells (P < 0.005). A maximal stimulatory concentration of isoproterenol (100 nM) leads to the same increment in ion flux in erythrocytes from hypothyroid and normal turkeys. Analysis of the quantitative relationship between isoproterenol concentration, receptor occupancy, and associated effects upon potassium influx shows that at low levels of isoproterenol, where occupancy is linear with agonist concentration, occupation of a given number of beta receptors leads to a stimulation of potassium transport that is identical in erythrocytes from normal and hypothyroid turkeys. Thus, decreased sensitivity to catecholamine-stimulated potassium transport in hypo-

The Influence of Hyperthyroidism and Hypothyroidism on α and β-Adrenergic Receptor Systems and Adrenergic Responsiveness*

“…6 Ka for isoproterenol unchanged. mal cells (67). This observation indicates that a greater fractional receptor occupancy is required in hypothyroid cells than in normal cells for a given absolute level of stimulated ion transport.…”

“…This observation indicates that a greater fractional receptor occupancy is required in hypothyroid cells than in normal cells for a given absolute level of stimulated ion transport. Quantitative analysis of the concentration-response curves, however, indicates that, for any absolute level of receptor occupancy at the low concentrations of isoproterenol required for the transport response (half-maximal at only 2-3% receptor occupancy), the magnitude of the transport response is, in fact, identical in normal and hypothyroid cells (67). Because, at low concentrations of isoproterenol, absolute receptor occupancy itself is linear with both isoproterenol concentration and total receptor number, the observed 50% reduction in /?…”

“…It was further reported in the same study that there was no detectable accumulation of cellular cyclic AMP in adipose tissue from hypothyroid rats even at maximal concentrations of 0 agonist. Like the reduced sensitivity of the physiological 0-adrenergic response of the hypothyroid turkey erythrocyte (enhancement of monovalent cation co-transport), the sensitivity of the physiological response of the fat cell (lipolysis) is also reduced under hypothyroid conditions, while both responses can be stimulated at high agonist concentratons to the same maximal levels that are attainable in cells from normal animals (40,67). In contrast to the preceding observations in the hypothyroid rat reticulocyte, the amount of ADP-ribosylatable guanine nucleotide-binding protein in hypothyroid rat adipose tissue was found to be only minimally increased (69), thereby implying that changes at this site do not account for the reduced sensitivity of this tissue to /?…”