ABSTRACT
The melanocortin-3 receptor (MC3R) is known to be involved in regulation of energy homeostasis, regulating feed efficiency and nutrient partitioning in mammals. Its physiological roles in non-mammalian vertebrates, especially economically important aquaculture species, are not well understood. Channel catfish (Ictalurus punctatus) is the main freshwater aquaculture species in North America. In this study, we characterized the channel catfish MC3R. The mc3r of channel catfish encoded a putative protein (ipMC3R) of 367 amino acids. We transfected HEK293T cells with ipMC3R plasmid for functional studies. Five agonists, including adrenocorticotropin, α-melanocyte stimulating hormone (α-MSH), ß-MSH, [Nle4, D-Phe7]-α-MSH, and D-Trp8-γ-MSH, were used in the pharmacological studies. Our results showed that ipMC3R bound ß-MSH with higher affinity and D-Trp8-γ-MSH with lower affinity compared with human MC3R. All agonists could stimulate ipMC3R and increase intracellular cAMP production with sub-nanomolar potencies. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation could also be triggered by ipMC3R. The ipMC3R exhibited constitutive activities in both cAMP and ERK1/2 pathways, and Agouti-related protein served as an inverse agonist at ipMC3R, potently inhibiting the high basal cAMP level. Moreover, we showed that melanocortin receptor accessory protein 2 (MRAP2) preferentially modulated ipMC3R in cAMP production rather than ERK1/2 activation. Our study will assist further investigation of the physiological roles of the ipMC3R, especially in energy homeostasis, in channel catfish.
Subject(s)
Energy Metabolism , Homeostasis , Ictaluridae/metabolism , Receptor, Melanocortin, Type 3/metabolism , Amino Acid Sequence , Animals , Base Sequence , Chromosomes/genetics , Cyclic AMP/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , HEK293 Cells , Homeostasis/drug effects , Humans , Ligands , Phylogeny , Receptor, Melanocortin, Type 3/chemistry , Receptor, Melanocortin, Type 3/genetics , Sequence Analysis, DNA , Signal Transduction , Synteny/geneticsABSTRACT
Neuropeptide S receptor 1 (NPSR1), originally named G protein-coupled receptor 154 (GPR154), was deorphanized in 2002 with neuropeptide S identified as the endogenous ligand. NPSR1 is primarily expressed in bronchus, brain as well as immune cells. It regulates multiple physiological processes, including immunoregulation, locomotor activity, anxiety, arousal, learning and memory, and food intake and energy balance. SNPs of NPSR1 are significantly associated with several diseases, including asthma, anxiolytic and arousal disorders, and rheumatoid arthritis. This chapter will summarize studies on NPSR1, including its molecular structure, tissue distribution, physiology, pharmacology, and pathophysiology.
