PINEAL BETA-ADRENERGIC RECEPTOR - CORRELATION OF BINDING OF L-ALPRENOLOL-H-3 WITH STIMULATION OF ADENYLATE-CYCLASE

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  • 1 January 1976
    • journal article
    • research article
    • Vol. 196  (3) , 714-722
Abstract
3H-l-Alprenolol, a potent competitive .beta.-adrenergic antagonist, binds to sites in rat pineal gland membranes. The properties of these binding sites were compared to those of the receptors which mediate the .beta.-adrenergic activation of pineal adenylate cyclase. Both sites are highly sterospecific. The l-stereoisomers of alprenolol and propranolol were at least 2 orders of magnitude more potent than the d-stereoisomers in inhibiting isoproterenol-stimulated adenylate cyclase or 3H-l-alprenolol binding. The dissociation constants (Kd) of the l-stereoisomers of both alprenolol and propranolol were 10-22 nM as determined by competition for binding sites or by inhibition of isoproterenol-stimulated adenylate cyclase. .beta.-adrenergic agonists which stimulated adenylate cyclase also competitively inhibited the binding of 3H-l-alprenolol. They showed the same order of potency (isoproterenol) > norepinephrine .gtoreq. epinephrine) and the same individual affinities in the 2 systems. .alpha.-Adrenergic blockers were ineffective in inhibiting either adenylate cyclase stimulation or 3H-l-alprenolol binding. Isoproterenol stimulation of adenylate cyclase activity, and 3H-l-alprenolol binding, were rapid and rapidly reversible. The 3H-l-alprenolol binding sites were saturable and bound 0.6 pmol of ligand/mg of added protein. The binding of 3H-l-alprenolol occurs at sites indistinguishable from the pineal .beta.-adrenergic receptor.