Recently, several workers have shown that adrenergic control of hepatic carbohydrate metabolism has the characteristics of an α-receptor-mediated process. Using the rat liver membrane preparation of Neville (Neville, D, (1968) Biochim. Biophys. Acta 154, 540-552), α-adrenergic receptors have been identified using the ligand [3H]dihydroergocryptine. The receptors are saturable and of high affinity. Scatchard analysis yields a K(D) 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 (α-adrenergic potency series: (-)-epinephrine > (-)-norepinephrine > (-)-isoproterenol. (-)-Isomers are more potent than (+)-isomers. The α-blocker phentolamine is 3.4 orders of magnitude more potent than the β-blocker propranolol. To determine subcellular localization of α-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 activity 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 α-adrenergic receptors are likely concentrated in the plasma membranes.
|Original language||English (US)|
|Number of pages||5|
|Journal||Journal of Biological Chemistry|
|State||Published - Dec 1 1978|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology