Rat pineal alpha 1-adrenoceptors: identification and characterization using [125I]iodo-2-[beta-(4-hydroxyphenyl)-ethylaminomethyl]tetralone.

[125I]Iodo-2-[beta-(4-hydroxyphenyl)-ethylaminomethyl]tetralone ([125I]HEAT), a selective, high affinity, high specific activity alpha 1-adrenoceptor ligand, is used to characterize alpha-adrenoceptors in the rat pineal gland. Binding of [125I]HEAT to membranes is rapid [association rate constant (Kon) = 3.1 nM-1 min-1] and readily reversible either by 100-fold dilution or by addition of excess unlabeled HEAT [apparent dissociation rate constant (Koff) = 0.153 min-1). Saturation experiments indicate a single class of noncooperative binding sites with an equilibrium binding constant (KD) of 41 +/- 9 pM and a Bmax of 399 +/- 63 fmol/mg protein. The relative potency of a number of adrenoceptor agonists and antagonists in competing with [125I] HEAT indicates the receptor is an alpha 1-subtype. In addition, inhibition of binding is stereospecific; (-)epinephrine and norepinephrine are more than 100-fold more potent than their (+)isomers. The identification of alpha 1-adrenoceptors in the pineal gland is consistent with evidence indicating a role for these receptors in the regulation of melatonin synthesis and phosphatidylinositol turnover.