2-Phenylmelatonin is an antagonist of the MEL-1A-R, MEL-1B-R, MT3, observed to demonstrate mixed antagonist/agonist activity in systems with differential expression of the receptor subtypes. In rabbit parietal cortex tissue characterized by the presence of MEL-1A-R/MEL-1B-R receptors, 2-Phenylmelatonin antagonized melatonin-induced inhibition of neuronal firing in only 80% of the neurons tested, prompting the investigators to suggest a mixed activity. In guinea pig colon cells expressing solely MT3 receptors, 2-phenylmelatonin demonstrates antagonism of melatonin-induced contractions at low (subnanomolar) concentrations, and shows partial agonist induction of contractility at higher (nanomolar/micromolar) concentrations. Comparable antagonism (at 0.01nM) to the MT3-specific antagonist Prazocin (sc-204858) in this system further supports direct interaction of 2-Phenylmelatonin at the MT3 receptor. In a mouse fibroblast NIH3T3 system expressing transfected human MEL1A-R (melatonin receptor), 2-Phenylmelatonin demonstrated full agonism comparable to the action of melatonin (sc-207848) itself. This differential mixed antagonist/agonist activity makes 2-Phenylmelatonin a particularly useful tool in studying melatonin receptor characteristics.
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