Some melanocortin receptors and the accessory protein MRAP1 have been found to interact in novel ways when co-expressed in the same cells following stimulation with either ACTH (1-24) or αMSH. These interactions have been seen for mammalian, bird, and some bony fish melanocortin receptors. Such analysis has not been done yet on the amphibian melanocortin receptors, MC1R, MC3R, MC4R, and MC5R. To this end, this study was done on the effects regarding ligand sensitivity for ACTH (1-24) and αMSH, when the MC1R, MC3R, MC4R, and MC5R paralogs of the amphibian, Xenopus tropicalis were expressed in Chinese Hamster Ovary cells either in the presence of absence of Gallus gallus (c) MRAP1. Based on previous studies on human MC1R, MC3R, MC4R, and MC5R, the expectation was that the sensitivity to stimulation by αMSH would be lower for all the X. tropicalis receptors. However, for every X. tropicalis receptor tested, co-expression with cMRAP1 had no negative or positive effect on sensitivity to stimulation by xtαMSH. In a similar manner co-expression of xtMC1R, MC3R, or MC5R with cMRAP1 had no effect, positive or negative, on stimulation with xtACTH(1-24). However, co-expression of xtMC4R with cMRAP1 did lower sensitivity to stimulation by xtACTH (1-24) in a statistically significant manner. To date, this type of negative interaction between an MC4R ortholog and an MRAP1 ortholog has not been reported for other vertebrates.

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