Abstract
The effects of the 5-HT4 receptor agonists BIMU 8, BIMU 1, renzapride and of the 5-HT1p receptor agonist 5-hydroxyindalpine on basal and electrically evoked outflow of tritium were studied in guinea-pig longitudinal muscle myenteric plexus preparations preincubated with [3H]choline. Muscle contractions were recorded simultaneously.
BIMU 8 caused a calcium dependent and tetrodotoxin sensitive increase in basal [3H]outflow that was assumed to represent release of [3H]acetylcholine. In addition, BIMU 8 enhanced the release of [3H]acetylcholine and twitch contractions evoked by submaximal electrical stimulation. Ondansetron (1 μmol/l) did not change the effects of BIMU 8, but DAU 6285 and tropisetron (each 1 μmol/l) competitively antagonized the various facilitatory effects of BIMU 8 with pA2 values of 7.0–7.2 (DAU 6285) and 7.0–7.3 (tropisetron). The phosphodiesterase inhibitors IBMX and rolipram did not increase the effects of BIMU 8. BIMU 1 and renzapride also concentration-dependently increased basal release of acetylcholine, and release and contractions caused by submaximal stimulation. The effects of BIMU 1 and renzapride were competitively antagonized by 1 μmol/l tropisetron (pA2 6.6–7.1). The EC50 values for the increase in the evoked [3H]acetylcholine release and contractions were closely similar. 5-Hydroxyindalpine did not change basal release and slightly inhibited the evoked release of [3H]acetylcholine. Release of acetylcholine and contractions elicited by submaximal stimulation were strongly inhibited by ( + )-tubocurarine which indicates that nicotinic ganglionic transmission is involved in this kind of release.
The results suggest that BIMU 8, BIMU 1 and renzapride stimulate 5-HT4 receptors at cholinergic interneurones and thereby facilitate nicotinic ganglionic transmission in the myenteric plexus. Cyclic AMP is probably not involved in the 5-HT4 receptor mediated facilitation of acetylcholine release.
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References
Baxter GS, Clarke DE (1992) Benzimidazolone derivatives act as 5-HT4 receptor ligands in rat oesophagus. Eur J Pharmacol 212:225–229
Baxter GS, Craig DA, Clarke DE (1991) 5-Hydroxytryptamine4 receptors mediate relaxation of the rat oesophageal tunica muscularis mucosae. Naunyn-Schmiedeberg's Arch Pharmacol 343:439–446
Beavo JA, Reifsnyder DH (1990) Primary sequence of cyclic nucleotide phosphodiesterase isozymes and the design of selective inhibitors. Trends Pharmacol Sci 11:150–155
Consolo S, Arnaboldi S, Giorgi S, Russi G, Ladinsky H (1994) 5-HT4 receptor stimulation facilitates acetylcholine release in frontal cortex. Neuroreport 5:1230–1233
Craig DA, Clarke DE (1990) Pharmacological characterization of a neuronal receptor for 5-hydroxytryptamine in guinea pig ileum with properties similar to the 5-hydroxytryptamine4 receptor. J Pharmacol Exp Ther 252:1378–1386
Dumuis A, Bouhelal R, Sebben M, Cory R, Bockaert J (1988) A nonclassical 5-hydroxytryptamine receptor positively coupled with adenylate cyclclase in the central nervous system. Mol Pharmacol 34: 880–887
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Kilbinger, H., Gebauer, A., Haas, J. et al. Benzimidazolones and renzapride facilitate acetylcholine release from guinea-pig myenteric plexus via 5-HT4 receptors. Naunyn-Schmiedeberg's Arch Pharmacol 351, 229–236 (1995). https://doi.org/10.1007/BF00233241
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DOI: https://doi.org/10.1007/BF00233241