Hepatic alpha-adrenergic receptors. Identification and subcellular localization using [3H]dihydroergocryptine.
Recently, several workers have shown that adrenergic control of hepatic carbohydrate metabolism has the characteristics of an alpha-receptor-mediated process. Using the rat liver membrane preparation of Neville (Neville, D. (1968) Biochim. Biophys. Acta 154, 540-552), alpha-adrenergic receptors have been identified using the ligand [3H]dihydroergocryptine. The receptors are saturable and of high affinity. Scatchard analysis yields a KD of 1.8 nM with 1.7 +/- 0.55 pmol of sites/mg of protein. Competition of dihydroergocryptine binding with various pharmacologic agents yields the typical (alpha-adrenergic potency series: (-)-epinephrine greater than (-)-norepinephrine greater than (-)-isoproterenol. (-)-Isomers are more potent than (+)-isomers. The alpha-blocker phentolamine is 3.4 orders of magnitude more potent than the beta-blocker propranolol. To determine subcellular localization of alpha-adrenergic receptors, livers were fractionated into a crude homogenate, a 1500 X g pellet, and the purified membrane preparation used previously for binding. Specific dihydroergocryptine binding, ouabain-inhibitable (Na,K)-ATPase, and F--stimulated adenylate cyclase activities, were followed in these fractions. Specific binding was enriched, relative to that in the crude homogenate, 2.88-fold in the pellet and 6.28-fold in the membranes. Similarly, (Na,K)-ATPase acticity was enriched 2.6-fold in the pellet and 7.1-fold in the membranes while adenylate cyclase activity was enriched 2.9-fold in the pellet and 3.5-fold in the membranes. It is concluded that hepatic alpha-adrenergic receptors are likely concentrated in the plasma membranes.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D004088:Dihydroergotoxine / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000302:isolation & purification / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D004088:Dihydroergotoxine; D000262:Adenylyl Cyclases