Alpha-adrenergic receptor regulation of Ca2+/Mg2+-ATPase in brain synaptic membranes.

The effects of alpha 1 and alpha 2-adrenergic receptor ligands on Ca2+/Mg2+-ATPase have been studied using synaptosomal plasma membranes isolated from rat brain cortex. Both phenylephrine and clonidine inhibited Ca2+/Mg2+-ATPase, in a concentration-dependent fashion. IC50 values for half-maximal inhibition for phenylephrine and clonidine were 29 microM and 18 microM, respectively. The inhibitory effect of phenylephrine was reversed by the alpha antagonist prazosin while yohimbine and rauwolscine reversed the inhibition of enzyme activity by clonidine. The two antagonist subtypes were effective only against the respective agonist subtypes, demonstrating distinct subtype preferences. Analysis of the kinetics of enzyme inhibition indicate both agonists to be noncompetitive. Some evidence suggests that yohimbine may exhibit mixed agonist/antagonist properties which depend on [Ca2+]. The present study provides biochemical evidence to support auto receptor alpha-adrenergic receptor regulation of neurotransmitter release.