Abstract
Previous reports from this laboratory have demonstrated that alpha 2-adrenergic receptors accelerate Na+/H+ exchange in NG108-15 neuroblastoma X glioma cells and evoke platelet secretion via a pathway involving Na+/H+ exchange. The present studies were designed to examine whether agents that interact with Na+/H+ antiporters also might influence alpha 2-adrenergic receptor-ligand interactions. We observed that Na+ decreases receptor affinity for the agonists epinephrine, norepinephrine, and UK14304 and slightly increases receptor affinity for the antagonists yohimbine and idazoxan in digitonin-solubilized preparations from porcine brain cortex. Increases in [H+] also decrease receptor affinity for agonists and cause either a slight increase or no change in receptor affinity for antagonists. Amiloride analogs accelerate the rate of [3H] yohimbine dissociation from digitonin-solubilized receptors with a relative effectiveness that parallels their ability to block Na+/H+ exchange in other systems. Interestingly, these modulatory effects of Na+,H+ and 5-amino-substituted analogs of amiloride are retained in homogeneous preparations of the alpha 2-adrenergic receptor, suggesting that the allosteric-binding sites for these agents are on the receptor-binding protein itself.
Highlights
From the Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232 and SMerck Sharp and Dohme Research Laboratories, West Point,Pennsylvania 19486. Previous reports from this laboratory have demon- and is retained in preparations of the a,adrenergic receptor strated thataz-adrenergicreceptors accelerate Na+/H+purified to apparent homogeneity by two sequential yohimexchange in NGlOS-15 neuroblastoma X glioma cells bine-agarose affinity chromatography steps
We observedthatNa+ decreases receptor affinity for the agonists epinephrine, The materials and methods used in the present studies are described in the Miniprint section of the accompanying paper (8)
The amiloride analogs were synthesized as described previreceptor affinity fortheantagonistsyohimbineand ously (9)
Summary
Vol 262, No 25, Issue of September 5, pp. 12387-12392,1987 Printed in U.S.A. Regulation of Porcine Brain a2-AdrenergicReceptors byNa+,H+and Inhibitors of Na+/H+ Exchange*. From the Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232 and SMerck Sharp and Dohme Research Laboratories, West Point,Pennsylvania 19486. Previous reports from this laboratory have demon- and is retained in preparations of the a,-adrenergic receptor strated thataz-adrenergicreceptors accelerate Na+/H+purified to apparent homogeneity by two sequential yohimexchange in NGlOS-15 neuroblastoma X glioma cells bine-agarose affinity chromatography steps
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