Adenylate-cyclase receptors for adrenergic neurotransmitters in rat cerebral cortex.

Abstract

The response of adenylate cyclase systems to putative neurotransmitter agents has been studied in cell‐free preparations from various brain regions of young adult rats. Homogenates of cerebral cortex contained adenylate cyclase systems which were responsive to norepinephrine and dopamine. A large proportion of this catecholamine‐sensitive adenylate cyclase activity was concentrated in the crude mitochondrial fraction. Adenylate cyclase activity in this fraction was also responsive to epinephrine and isoproterenol, showed very small stimulation with histamine and serotonin, and was unresponsive to acetylcholine and 4‐aminobutyric acid. The natural l‐forms of the catecholamines were much more active than the d‐forms. Adrenocorticotrophic hormone, glucagon, thyroid stimulating hormone and luteinizing hormone were without significant effect in the cerebral preparation. Basal values for adenylate cyclase activity and the degree of stimulation by the catecholamines were critically dependent upon appropriate concentrations of ATP, an ATP‐regenerating system, H+, Mg2+ and Ca2+ in the assay medium. Addition of the membrane phospholipids, phosphatidylserine and phosphatidylinositol, enhanced stimulation by the catecholamines. Concentrations of norepinephrine or dopamine as low as 0.005 mM produced significant increases in adenylate cyclase activity. The maximum response to norepinephrine was two to three times that with dopamine. The response of cerebral adenylate cyclase to 0.05 mM norepinephrine was strongly blocked by concentrations (0.1 mM) of the β‐adrenergic blocking agents, propranolol and dichloroisoproterenol, which had no effect on the response to 0.05 mM dopamine. Haloperidol eliminated the dopamine response at very low concentration (0.01 mM). The data suggest that norepinephrine and dopamine activate adenylate cyclase systems in rat cerebral cortex by reacting with specific receptors which have the properties of β‐adrenergic and dopaminergic receptors, respectively.