Receptor Reserves at α₂-adrenergic and Dopaminergic Autoreceptors

Abstract

Repeated observations that the maximal response elicited by an agonist can be obtained when only a fraction of receptors are occupied has led to the concept of “spare receptors” (or “receptor reserve”). A large pool of “spare receptors” has been found in many peripheral tissues and partial agonists with substantial, but submaximal, intrinsic efficacy often produce maximal response (Nickerson 1956; Stephenson 1956; Ariens et al., 1960). The law of mass action relates fractional occupancy to ligand concentration and it follows that a lower agonist concentration will suffice to elicit a particular level of response the greater the excess of functional receptors (larger receptor reserve). In order to delineate the relationship between receptor occupancy and closely coupled physiologic responses at α₂-adrenergic and dopaminergic autoreceptors, we have inactivated a portion of these receptors with the recently described irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) (Meller et al., 1985). This compound was found to dose-dependently inactivate central α₂-adrenrgic and dopaminergic receptors in vivo.