Identification of β-adrenergic receptors in rat hypothalamus

Abstract

(−)-[3H]Dihydroalprenolol((−)-[3H]DHA) binding in the rat hypothalamus appears to possess all the characteristics expected of physiologically relevant β-adrenergic receptors. Binding of (−)-[3H]DHA to the hypothalamic sites was rapid (k1 = 1.3 × 107 min−1M−1) and also rapidly reversible. Binding was saturable at low concentrations of ligand( ~ 50–100 nM). The dissociation constant (KD) of (−)-[3H]DHA binding determined by equilibrium analysis was 19 nM. Binding displayed β-adrenergic specificity. β-Adrenergic agonists inhibited binding in the following order of potency: (−)-isoproterenol [Formula: see text] (−)-epinephrine > (−)-norepinephrine. Specific β-adrenergic antagonists (−)-propranol and (−)-alprenolol inhibited binding at low concentrations (KD = 25–50 nM) whereas the α-antagonist phentolamine inhibited binding at very high concentrations (KD = 42 μM). Interactions of both agonists and antagonists with the sites showed stereoselectivity. The (−)-isomers of all β-adrenergic agents tested were more potent than their respective (+)-isomers. These results suggest that specific receptor sites for β-adrenergic catecholamines are present in rat hypothalamus.