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Pharmacology of the giant panda (Ailuropoda melanoleuca) melanocortin-3 receptor.
General and Comparative Endocrinology 2018 October 32
The melanocortin-3 receptor (MC3R) is a member of the G protein-coupled receptor superfamily that plays a critical role in controlling energy balance and metabolism. Although pharmacological characterization of MC3R has been reported previously in several other species, there is no report on the MC3R from giant panda (Ailuropoda melanoleuca). This ancient species is known as a 'living fossil' and is among the most endangered animals in the world. Giant panda survive on a specialized diet of bamboo despite possessing a typical carnivorous digestive system. We report herein the molecular cloning and pharmacological characterization of amMC3R. Homology and phylogenetic analysis showed that amMC3R was highly homologous (>85%) to several other mammalian MC3Rs. Using human MC3R (hMC3R) as a control, the binding of five agonists, [Nle4 , D-Phe7 ]-α-melanocyte stimulating hormone (NDP-MSH), α-, β-, γ-, and D-Trp8 -γ-MSH, was investigated, as well as Gs-cAMP and pERK1/2 signaling. The results showed that amMC3R bound NDP- and D-Trp8 -γ-MSH with the highest affinity, followed by α-, β-, and γ-MSH, with the same rank order as hMC3R. When stimulated with agonists, amMC3R displayed increased intracellular cAMP and activation of pERK1/2. These data suggest that the cloned amMC3R was a functional receptor. The availability of amMC3R and knowledge of its pharmacological functions will assist further investigation of its role in controlling energy balance and metabolism.
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