Inhibition of acetylcholine turnover rate in rat hippocampus and cortex by intraventricular injection of adenosine analogs

Thomas F. Murray, W. D. Blaker, D. L. Cheney, E. Costa

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Abstract

The effects of i.c.v. administration of adenosine receptor agonists and antagonists on the turnover rate of acetylcoline (TR(ACh)) in various areas of the rat brain were examined in an effort to better understand the role of adenosine as a neuromodulator or cotransmitter. TR(ACh) was determined by gas chromatographic-mass fragmentographic analysis of the rate of deuterium incorporation into ACh and choline during a constant rate infusion of deuterated phosphorylcholine. The i.c.v. administration of the adenosine receptor agonist, 2-chloroadenosine (2-ClAdo), in a dose of 83 nmol failed to change the ACh or choline content of any of the brain areas examined. This dose of 2-ClAdo elicited significant reductions in the TR(ACh) in both the hippocampus and frontal cortex, but not in the striatum. The extent of the TR(ACh) reduction was 67 and 36% in hippocampus and cortex, respectively. This inhibition of TR(ACh) elicited by 2-ClAdo was antagonized by pretreatment (i.c.v.) with theophylline (278 nmol), suggesting that an activation of adenosine receptors is operative in the action of 2-ClAdo. Further support for a participation of adenosine receptors in the action of 2-ClAdo was obtained by comparing the effects of the L- and D-isomers of phenylisopropyladenosine (PIA) on TR(ACh). The i.c.v. administration of L-PIA (65 nmol) elicited a 79% reduction in the TR(ACh) in the hippocampus, whereas D-PIA (65 nmol i.c.v.) had no significant effect on hippocampal TR(ACh). This finding supports the view that these effects on TR(ACh) may be mediated by adenosine A1 receptors, but not by A2 receptors, because the former, but not the latter, display marked stereoselectivity toward PIA. It also was demonstrated that intraseptal injections of L-PIA or theophylline failed to reduce the TR(ACh) in the hippocampus, suggesting that adenosine receptors located in the septum are not operative in mediating the i.c.v. action of PIA.

Original languageEnglish
Pages (from-to)550-554
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume222
Issue number3
Publication statusPublished - 1982
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Pharmacology

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