caa a22 4500 469079231 CHVBK 20180323132945.0 cr unu---uuuuu 170328e19920301xx s 000 0 eng 10.1007/BF00168686 doi (NATIONALLICENCE)springer-10.1007/BF00168686 Effects of 5-HT4 receptor stimulation on basal and electrically evoked release of acetylcholine from guinea-pig myenteric plexus [Elektronische Daten] [H. Kilbinger, D. Wolf] Summary: The effects of 5-methoxytryptamine and 5-hydroxytryptamine (5-HT) on both basal and electrically evoked outflow of tritium were studied in guinea-pig myenteric plexus preparations preincubated with [3H]-choline. Basal outflow. 5-Methoxytryptamine caused a transient and calcium-dependent increase in basal outflow of [3H]acetylcholine that was abolished by tetrodotoxin. Ondansetron (1 μmol/1) did not affect the stimulatory response of 5-methoxytryptamine but ICS 205-930 (1 and 3 μmol/1) produced parallel rightward displacements of the concentration-response curve to 5-methoxytryptamine. The PKB value for ICS 205-930 was 6.6 suggesting an involvement of 5-HT4 receptors. 5-HT caused an increase in basal outflow of [3H]acetylcholine and a biphasic concentration-response curve was obtained. The maximal response of the first phase to 5-HT (release of 0.98% of tissue tritium) and the maximal response to 5-methoxytryptamine (0.94% of tissue tritium) were similar but 5-methoxytryptamine (-log EC50: 6.9) was less potent than 5-HT (-log EC50 of the high affinity component: 7.9). ICS 205-930 (0.01-1.0 μmol/1) acted as a competitive antagonist against the low affinity component of the 5-HT concentration-response curve with a pA2 value of 8.0. It is concluded that stimulation of both 5-HT4 receptors (by 5-methoxytryptamine and submicromolar concentrations of 5-HT) and 5-HT3 receptors (by micromolar concentrations of 5-HT) causes a release of acetylcholine which in turn leads to smooth muscle contraction. Electrically evoked outflow. This outflow of [3H]acetylcholine was concentration-dependently inhibited by both 5-methoxytryptamine and 5-HT. ICS 205-930 (1 μmol/1) reinforced the inhibitory effect of 5-methoxytryptamine but not that of 5-HT. In the presence of methiothepine (0.1 μmol/1) 5-methoxytryptamine enhanced the evoked outflow of [3H]acetylcholine, an effect which was attenuated by 3 μmol/1 ICS 205-930. These results suggest that 5-methoxytryptamine may both inhibit (via 5-HT1 receptors) and facilitate (via 5-HT4 receptors) the evoked release of acetylcholine from guinea-pig myenteric neurones. The facilitatory action is unmasked when the 5-HT1 receptor is blocked by methiothepine. Springer-Verlag, 1991 5-Methoxytryptamine nationallicence 5-Hydroxytryptamine nationallicence 5-HT4 receptor nationallicence 5-HT3 receptor nationallicence Acetylcholine release nationallicence Guinea pig ileum nationallicence Kilbinger H. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, W-6500, Mainz, Federal Republic of Germany aut Wolf D. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, W-6500, Mainz, Federal Republic of Germany aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/3(1992-03-01), 270-275 0028-1298 345:3<270 1992 345 210 https://doi.org/10.1007/BF00168686 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00168686 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kilbinger H. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, W-6500, Mainz, Federal Republic of Germany aut NATIONALLICENCE 700 1- Wolf D. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, W-6500, Mainz, Federal Republic of Germany aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/3(1992-03-01), 270-275 0028-1298 345:3<270 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer