title: Regulation of porcine brain alpha 2-adrenergic receptors by Na+,H+ and inhibitors of Na+/H+ exchange.
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.
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry; D000068438:Brimonidine Tartrate; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D002540:Cerebral Cortex / Q000032:analysis; D004837:Epinephrine / Q000494:pharmacology; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D011810:Quinoxalines / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers; D013552:Swine; D015016:Yohimbine / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D017923:Sodium-Hydrogen Exchangers; D015016:Yohimbine; D000068438:Brimonidine Tartrate; D000584:Amiloride; D006859:Hydrogen; D012964:Sodium; D004837:Epinephrine