2-phenylmelatonin: A partial agonist at enteric melatonin receptors

The effect of the melatonin receptor ligand, 2-phenylmelatonin, has been as sessed in isolated strips of the guineapig proximal colon. 2-Phannylmelaton in (0.01 nM-1 muM) caused a concentration-dependent contractile response. T he potency value (- log EC50) was 9.3 +/- 1.0. The maximum effect was 25 +/ - 4% of that elicited by the maximally effective concentration (0.3 muM) of 5-HT and 43 +/- 3% of that by the maximally effective concentration (10 mu M) of melatonin. When used as an antagonist, 2-phenylmelatonin (0.01 nM and 0.1 nM) concentration-dependently inhibited melatonin-induced contractions with depression of the maximum response by 25% and 54%, respectively. High er (I nM) 2-phenylmelatonin concentrations failed to antagonize melatonin-i nduced response. Prazosin (0.3 muM), a selective antagonist of melatonin MT 3 sites, antagonized melatonin-induced contractions to an extent similar to that induced by 0.01 nM t-phenylmelatonin (with 30% reduction of the maxim um effect to melatonin). The combination of 0.3 muM prazosin and 0.01 nM 2- phenylmelatonin caused antagonism similar in extent to that caused by each individual antagonist. 2-Phenylmelatonin at subnanomolar concentrations beh aves as an antagonist of melatonin-induced contractile responses while at n anomolar/micromolar concentrations it behaves as a weak contractile agonist .