Cyclic AMP-generating systems: Regional differences in activation by adrenergic receptors in rat brain

Abstract

Catecholamine, histamine, and adenosine-mediated accumulations of radioactive cyclic AMP were assessed in adenine-labeled slices from eight rat brain regions. 2-Fluoronorepinephrine, a selective β-adrenergic agonist, elicited an accumulation of cyclic AMP in cerebral cortex, cerebellum, hippocampus, striatum, superior colliculi, thalamus, hypothalammus, and medulla-pons. In cerebral cortex and most other brain regions, the β-adrenergic-mediated response appeared to involve primarily β1-adrenergic receptors, while in cerebellum, there was a significant involvement of β2-adrenergic receptors. 6-Fluoronorepinephrine, a selective α-adrenergic agonist, elicited accumulations of cyclic AMP in all regions except cerebellum. Combinations of the two fluoro derivatives afforded in all brain regions an accumulation of cyclic AMP identical with that elicited by norepinephrine. In hypothalamus, the α- and β-adrenergic responses were significantly greater than additive. In cerebral cortex, the α-adrenergic receptor-mediated response appeared to involve α1-adrenergic receptors and to be nearly completely dependent on adenosine, while in other brain regions, the dependence of the α-adrenergic response on adenosine was less or absent. Combinations of 6-fluoronorepinephrine and histamine had greater than additive effects in cortex and hippocampus. The results indicate that the interactive control of cyclic AMP-generating systems by α-adrenergic, β-adrenergic, adenosine, and histamine receptors differs significantly among rat brain regions.