Further evidence for a glial localization of rat cortical beta-adrenoceptors: studies of in vivo cyclic AMP responses to catecholamines.
The present experiments were designed to clarify the cellular localization of postsynaptic beta-receptors in the rat cortex by studying the cellular source and pharmacological characteristics of in vivo cAMP responses to catecholamines. The method used to study in vivo cAMP responses in the brain involved microdialysis both to deliver catecholamines to cerebral tissue and to sample cAMP released in response to local beta-receptor activation. It was found that selective blockade of the metabolism of glial cells by fluorocitrate infusion produced a virtually complete (90%) inhibition of the cortical cAMP response to norepinephrine (NE). Selective damage of neurons by kainic acid infusion had little effect on the response. Pharmacological experiments showed that the response was selectively antagonized by a beta 1-receptor blocker which also selectively antagonized the cAMP response to NE in brain slices known to be localized in glial cells. These results support the hypothesis that beta-adrenoceptors of the rat cortex are predominantly localized on glial cells and therefore strongly suggest that these cells are an important target of the locus coeruleus noradrenergic system.
Stone
E A
EA
Department of Psychiatry, New York University Medical Center, NY 10016.
John
S M
SM
D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D002951:Citrates / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D009778:Occipital Lobe / Q000502:physiology; D010296:Parietal Lobe / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D002951:Citrates; D011943:Receptors, Adrenergic, beta; C007744:fluorocitrate; D000242:Cyclic AMP; D007608:Kainic Acid; D009638:Norepinephrine