β-Adrenergic activity of (±)-hydroxybenzylisoproterenol in isolated rat fat cells and hepatocytes

Abstract

The pharmacology of (±)-hydroxybenzylisoproterenol with respect to stimulation of cyclic AMP accumulation by isolated rat fat cells and liver cells was examined. (±)-Hydroxybenzylisoproterenol was found to be a full agonist and twice as potent as (−)-isoproterenol in liver cells, and equipotent to (−)-isoproterenol in fat cells with regard to stimulating cyclic AMP accumulation. A study of the ability of this catecholamine to stimulate adenylate cyclase activity of broken-cell preparations revealed that (±)-hydroxybenzylisoproterenol was equipotent to (−)-isoproterenol in liver cell homogenates, while 3- to 4-fold more potent than (−)-isoproterenol in fat cell ghost membranes. (±)-Hydroxybenzylisoproterenol was also found to be as potent as (−)-isoproterenol in stimulating cyclase activity of S49 mouse lymphoma cell membranes. Competition studies of specific [ 125I]iodohydroxybenzylpindolol binding to liver cell membranes revealed a K d of 10 nM for (±)-hydroxybenzylisoproterenol and 25 nM for (−)-isoproterenol binding to the liver β-adrenergic receptor. Competition studies of specific (−)-[ 3H]dihydroalprenolol binding to fat cell membranes indicated a similar affinity of these sites for both (±)-hydroxybenzylisoproterenol and (−)-isoproterenol. The guanyl nucleotide Gpp(NH)p induced a shift in the curve for competition of (−)-[ 3H]dihydroalprenolol binding by (−)-isoproterenol to the right, but failed to do so when (±)-hydroxybenzylisoproterenol was the competing agonist. Properties of (±)-[ 3H]hydroxybenzylisoproterenol binding to fat cell or liver cell membranes were inconsistent with those expected of adenylate cyclase coupled β-adrenergic receptors.