3H]Spiroperidol (Spiperone) Binding to a Putative Dopamine Receptor in Sheep and Steer Pituitary and Stalk Median Eminence*

Abstract

The dopamine antagonist [3H]spiroperidol (spiperone) binds with high affinity to one class of sites in the sheep and steer anterior pituitary, posterior pituitary, and stalk median eminence. The specific binding in the anterior pituitary of the sheep satisfies all criteria studied for a receptor, including high affinity binding (dissociation constant = 0.85 nM for sheep and 0.38 nM for steer), saturability (sites = 343 fmol/mg protein for sheep and 210 fmol/mg for steer), temperature dependence, and reversibility. The rank order of potency of various agonists to compete with [3H]spiroperidol for the sites in the sheep anterior pituitary is consistent with interactions at a dopamine receptor (i.e. bromergocryptine > apomorphine > dopamine > norepinephrine ≥ epinephrine). Furthermore, this potency series parallels that seen for the inhibition of PRL secretion from the anterior pituitary in vitro. Dopamine metabolites, β-endorphin, TRH, and the catecholestrogen methoxyestrone did not compete for [3H]spiroper...