MULTIPLE ADRENERGIC-RECEPTOR SUBTYPES CONTROLLING CYCLIC-AMP FORMATION - COMPARISON OF BRAIN-SLICES AND PRIMARY NEURONAL AND GLIAL CULTURES

The adrenergic receptor subtypes involved in cyclic AMP responses to norepinephrine (NE) were compared between slices of rat cerebral cortex and primary neuronal and glial cultures from rat brain. In neuronal cultures, NE and the beta-adrenergic receptor agonist isoproterenol (ISO) caused similar increases in cyclic AMP, which were not altered by the alpha-adrenergic receptor antagonist phentolamine. In glial cultures, NE caused a much smaller cyclic AMP response than did ISO, and this difference was reversed by alpha-adrenergic receptor antagonists (phentolamine > yohimbine > prazosin). alpha-2-Adrenergic receptor agonists partially inhibited the ISO response in glial cultures to a level similar to that observed with NE alone (clonidine = UK 14,304 > NE > 6-fluoro-NE > epinephrine). In slices from cerebral cortex, NE caused a much larger increase in cyclic AMP than did ISO, and this difference was reversed by alpha-adrenergic receptor antagonists with a different order of potency (prazosin > phentolamine > yohimbine). alpha-1-Adrenergic receptor agonists potentiated the response to ISO to a level similar to that observed with NE alone (epinephrine = NE > phenylephrine > 6-fluoro-NE > methoxamine). In all three tissue preparations, large responses to both alpha-1-receptor activation (increases in inositol phosphate accumulation) and alpha-2-receptor activation (decreases in forskolin-stimulated cyclic AMP accumulation) were observed. These data indicate that all of the major adrenergic receptor subtypes (beta, alpha-1, alpha-2) are present in each tissue preparation. However, the cyclic AMP response to NE is mediated through beta-adrenergic receptors in neuronal cultures, through combinations of beta- and alpha-2-adrenergic receptors in glial cultures, and through combinations of beta- and alpha-1-adrenergic receptors in cortical slices.