Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, United States.
Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, United States; Institute of Applied Biotechnology, Life Science and Technology School, Lingnan Normal University, Zhanjiang 524048, Guangdong, China.
Gen Comp Endocrinol. 2023 Feb 1;332:114180. doi: 10.1016/j.ygcen.2022.114180. Epub 2022 Nov 28.
The mammalian melanocortin-5 receptors (MC5Rs) are involved in various functions, including exocrine gland secretion, glucose uptake, adipocyte lipolysis, and immunity. However, the physiological role of fish Mc5r is rarely studied. Melanocortin-2 receptor accessory protein 2 (MRAP2) modulates pharmacological properties of melanocortin receptors. Herein, to lay the foundation for future physiological studies, we cloned the orange-spotted grouper (Epinephelus coioides) mc5r, with a 1008 bp open reading frame and a predicted protein of 334 amino acids. Grouper mc5r had abundant expression in the brain, skin, and kidney. Four ligands could bind to grouper Mc5r and dose-dependently increase intracellular cAMP levels. Grouper Mrap2 did not affect binding affinity or potency of Mc5r; however, grouper Mrap2 decreased cell surface expression and maximal binding of Mc5r. Mrap2 also significantly decreased the maximal response to a superpotent agonist but not the endogenous agonist. This study provided new data on fish Mc5r pharmacology and its regulation by Mrap2.
哺乳动物的黑皮质素-5 受体（MC5Rs）参与各种功能，包括外分泌腺分泌、葡萄糖摄取、脂肪细胞脂肪分解和免疫。然而，鱼类 Mc5r 的生理作用很少被研究。黑皮质素-2 受体辅助蛋白 2（MRAP2）调节黑皮质素受体的药理学特性。在此，为未来的生理研究奠定基础，我们克隆了橙色斑点石斑鱼（Epinephelus coioides）的 mc5r，其开放阅读框为 1008bp，预测蛋白为 334 个氨基酸。石斑鱼 mc5r 在大脑、皮肤和肾脏中大量表达。四种配体可以与石斑鱼 Mc5r 结合，并剂量依赖性地增加细胞内 cAMP 水平。石斑鱼 Mrap2 不影响 Mc5r 的结合亲和力或效力；然而，石斑鱼 Mrap2 降低了 Mc5r 的细胞表面表达和最大结合。Mrap2 还显著降低了对超效激动剂的最大反应，但对内源性激动剂没有影响。本研究为鱼类 Mc5r 药理学及其受 Mrap2 调节提供了新的数据。
