Involvement of GABA systems in acetylcholine release induced by 5-HT3 receptor blockade in slices from rat entorhinal cortex.
The aim of the present study was to examine the role of 5-HT3 receptors in spontaneous and K(+)-evoked acetylcholine (ACh) release from rat entorhinal cortex and striatal slices. The 5-HT3 receptor antagonists ondansetron and granisetron (0.01-10 microM) produced a concentration-dependent increase in both spontaneous and K(+)-evoked [3H]ACh release in the two brain regions studied. The release of ACh was Ca(2+)-dependent and tetrodotoxin-sensitive. 5-HT3 receptor agonists, such as 2-methyl-5-HT and 1-phenylbiguanide, at concentrations up to 1 microM, did not show any intrinsic effect on [3H]ACh release in both rat brain regions. However, 2-methyl-5-HT, 1 microM, fully blocked the ondansetron-induced enhancement in both basal and K(+)-evoked ACh release, suggesting that 5-HT, through 5-HT3 receptor activation, tonically inhibits ACh release. The possible implication of interposed inhibitory systems in ACh release after 5-HT3 receptor blockade was subsequently analyzed. While the effect of ondansetron was not modified by haloperidol or naloxone, the GABAA receptor antagonist bicuculline produced a marked potentiation of ACh release in the entorhinal cortex but not in the striatum. The results suggest that in this cortical area 5-HT activates 5-HT3 receptors located on GABAergic neurons which in turn inhibit cholinergic function.
Ramírez
M J
MJ
Department of Pharmacology, School of Medicine, University of Navarra, Pamplona, Spain.
Cenarruzabeitia
E
E
Lasheras
B
B
Del Río
J
J
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology; D018728:Entorhinal Cortex / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018678:Cholinergic Agents; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine; D011188:Potassium