Multiple Adrenergic Receptor Subtypes Controlling Cyclic AMP Formation: Comparison of Brain Slices and Primary Neuronal and Glial Cultures

Abstract

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 greater than yohimbine greater than 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 greater than NE greater than 6-fluoro-NE greater than 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 greater than phentolamine greater than yohimbine). alpha 1-Adrenergic receptor agonists potentiated the response to ISO to a level similar to that observed with NE alone (epinephrine = NE greater than phenylephrine greater than 6-fluoro-NE greater than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Noradrenaline enhances monocarboxylate transporter 2 expression in cultured mouse cortical neurons via a translational regulation

“…A similar enhancement of MCT2 expression was obtained following dBcAMP or forskolin exposure. As NA is known to induce cAMP formation in cultured neurons via the activation of β‐adrenergic receptors (Atkinson and Minneman 1991), these results suggest that the effect of NA could be mediated via cAMP formation and protein kinase A activation. In contrast to protein expression, no effect of either NA, dBcAMP or forskolin was observed on MCT2 mRNA expression.…”

Thyroid Hormone Homeostasis in Brain: Possible Involvement of Adrenergic Phenomenon in Adult Rat

“…Although CLON is an α 2 -AR agonist, there are a number of psychopharmacological studies in which clonidine’s profile does not correspond to α 2 -AR stimulation but rather conforms to that of an α 1 -AR agonist [30, 31]. α 1 -AR is linked to G q and activates phospholipase C, resulting in the production of inositol trisphosphate (IP 3 ) and diacylglycerol from phosphoinositol bisphosphate, with a consequent rise in intracellular [Ca 2+ ] i [17, 32, 33] derived from the intracellular calcium storage sites [34]. In fact, we observed a high increase in [Ca 2+ ] i on Day 20.…”

7?-hydroxysterol is cytotoxic to neonatal rat astrocytes in primary culture when cAMP levels are increased

“…Intracellular cAMP levels were increased either by using a cAMP analog, dbcAMP, or by receptor-mediated activation of adenylate cyclase. The presence of adrenergic receptors both on cultured astrocytes (Atkinson and Minneman, 1991) and on astrocytes in normal and lesioned adult brain (Mantyh et al, 1995) is well documented; moreover, the density of ␤-adrenergic receptors is increased on reactive astrocytes (Shao and McCarthy, 1994). We thus have used isoproterenol to differentiate astrocytes in vitro.…”