Identification of beta adrenergic receptors in rat hypothalamus.
(-)-[3H]-Dihydroalprenolol((-)[3H]DHA) binding in the rat hypothalamus appears to possess all the characteristics expected of physiologically relevant beta-adrenergic receptors. Binding of (-)-[3H]DHA to the hypothalamic sites was rapid (k1 = 1.3 X 10(-7) min-1) and also rapidly reversible. Binding was saturable at low concentrations of ligand (approximately 50-100 nM). The dissociation constant (KD) of (-)-[3H]DHA binding determined by equilibrium analysis was 19 nM. Binding displayed beta-adrenergic specificity. beta-Adrenergic agonists inhibited binding in the following order of potency: (-)-isoproterenol congruent to (-)-epinephrine greater than (-)-norepinephrine. Specific beta-adrenergic antagonists (-)-propranol and (-)-alprenolol inhibited binding at low concentrations (KD = 25-50nM) whereas the alpha-antagonist phentolamine inhibited binding at very high concentration (KD = 42 micron). Interactions of both agonists and antagonists with the sites showed stereoselectivity. The (-)-isomers of all beta-adrenergic agents tested were more potent than their respective (+)-isomers. These results suggest that specific receptor sites for beta-adrenergic catecholamines are present in rat hypothalamus.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000526:Alprenolol / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D000526:Alprenolol; D012110:Reserpine