2-Phenylmelatonin: a partial agonist at enteric melatonin receptors.
The effect of the melatonin receptor ligand, 2-phenylmelatonin, has been assessed in isolated strips of the guinea-pig proximal colon. 2-Phenylmelatonin (0.01 nM-1 microM) caused a concentration-dependent contractile response. The 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 microM) of 5-HT and 43 +/- 3%, of that by the maximally effective concentration (10 microM) 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. Higher (1 nM) 2-phenylmelatonin concentrations failed to antagonize melatonin-induced response. Prazosin (0.3 microM), a selective antagonist of melatonin MT3 sites, antagonized melatonin-induced contractions to an extent similar to that induced by 0.01 nM 2-phenylmelatonin (with 30% reduction of the maximum effect to melatonin). The combination of 0.3 microM prazosin and 0.01 nM 2-phenylmelatonin caused antagonism similar in extent to that caused by each individual antagonist. 2-Phenylmelatonin at subnanomolar concentrations behaves as an antagonist of melatonin-induced contractile responses while at nanomolar/micromolar concentrations it behaves as a weak contractile agonist.
Santagostino-Barbone
M G
MG
Department of Experimental and Applied Pharmacology, School of Pharmacy, University of Pavia, Italy.
Masoero
E
E
Spelta
V
V
Lucchelli
A
A
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D003106:Colon / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000819:agonists*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D044094:Receptors, Melatonin; D012701:Serotonin / Q000494:pharmacology
C100536:2-phenylmelatonin; D000317:Adrenergic alpha-Antagonists; D016166:Free Radical Scavengers; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D012701:Serotonin; D008550:Melatonin; D011224:Prazosin