5-HT3 receptor ligands lack modulatory influence on acetylcholine release in rat entorhinal cortex.
The objective of this study was to explore the role of 5-HT3 receptors in modulating potassium (K+)-evoked release of [3H]-acetylcholine ([3H]-ACh) from superfused slices of rat entorhinal cortex previously loaded with [3H]-choline. Rat entorhinal cortices were cross-chopped into 300 microns slices, superfused with oxygenated Krebs buffer containing 2.5 mmol/l Ca2+ and stimulated with two consecutive exposures of 20 mmol/l K+ for 4 min (S1 and S2, respectively). Compounds were added 20 min before S2 stimulation and remained in the superfusion buffer for the duration of the experiment. The S2/S1 ratio was then calculated. Stimulated release of [3H]-ACh was dependent on extracellular Ca2+ and K+ concentration. In Sprague Dawley rats, 2-methyl-5-HT (10(-9)-10(-6) mol/l), in the presence of 1 mumol/l ritanserin or 1 mumol/l ondansetron, had no influence on K(+)-evoked release of [3H]-ACh. In slices prepared from Hooded Lister rats, 2 mumol/l 5-HT but not 2-Me-5-HT significantly (P < 0.05) inhibited K(+)-evoked [3H]-ACh release only 17% in the presence of 1 mumol/l ritanserin. However, 2 mumol/l 2-Me-5-HT plus 1 nmol/l ondansetron had no effect. High performance liquid chromatography coupled to electrochemical detection (HPLC-ECD) was used to monitor endogenous release of ACh in the above conditions to confirm data from the radiolabelled experiments. No significant inhibition or increase in K(+)-evoked ACh release was observed with either 5-HT3 receptor agonists or antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Johnson
R M
RM
Department of Neurosciences, Syntex Discovery Research, Palo Alto, CA 94304.
Inouye
G T
GT
Eglen
R M
RM
Wong
E H
EH
D000109:Acetylcholine / Q000378:metabolism*; D000375:Aging / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009833:Olfactory Pathways / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D017366:Serotonin Receptor Agonists; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium