Activation of cholinergic and adrenergic receptors increases the concentration of extracellular adenosine in the cerebral cortex of unanesthetized rat.
Adenosine is an inhibitory neuromodulator in the CNS. For extracellular adenosine to play a physiological role in the brain, it must be present at effective concentrations. Acetylcholine and noradrenaline are known to play an important role in modulating the activity of cortical neurons, and they might have a role also in the release of adenosine in the cerebral cortex in vivo. We examined whether activation of cholinergic and adrenergic receptors affects extracellular adenosine levels in the cerebral cortex of unanesthetized rats using in vivo microdialysis. All drugs were administered locally within the cortex by reverse dialysis. Both acetylcholine and the acetylcholinesterase inhibitor neostigmine increased extracellular adenosine levels, and the effect of neostigmine was blocked by the nicotinic receptor antagonist mecamylamine. Both nicotine and the nicotinic receptor agonist epibatidine increased the concentration of extracellular adenosine. Activation of muscarinic receptors using the nonselective agonist oxotremorine and a selective M1 receptor agonist also increased extracellular adenosine levels. Noradrenaline and the noradrenergic reuptake inhibitor desipramine increased extracellular adenosine levels. The alpha(1)-adrenergic receptor agonist phenylephrine and the beta-adrenergic agonist isoproterenol increased extracellular adenosine levels, whereas the alpha(2)-adrenergic receptor agonist clonidine did not have an effect. These findings indicate that activation of specific cholinergic and adrenergic receptors can increase extracellular levels of adenosine in the cortex, and suggest that cholinergic and adrenergic receptor-mediated regulation of adenosine levels may represent a mechanism for controlling the excitability of cortical neurons.
Bennett
H J
HJ
Department of Anatomy and Neurobiology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 1X5, Canada.
White
T D
TD
Semba
K
K
D000241:Adenosine / Q000096:biosynthesis / Q000378:metabolism*; D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D018679:Cholinergic Agonists / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism*; D014851:Wakefulness
D000322:Adrenergic Agonists; D018679:Cholinergic Agonists; D011941:Receptors, Adrenergic; D011950:Receptors, Cholinergic; D000241:Adenosine