Melanocortin-4 Receptor in Spotted Sea Bass, Lateolabrax maculatus: Cloning, Tissue Distribution, Physiology, and Pharmacology
Melanocortin-4 receptor (MC4R) plays important roles in regulation of multiple physiological processes including energy homeostasis, reproduction, sexual function, and other functions in mammals. Recent studies suggested that teleost MC4Rs have different physiological functions and pharmacological c...
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| Format: | Article |
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Frontiers Media S.A.
2019-10-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2019.00705/full |
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| author | Kai-Qiang Zhang Zhi-Shuai Hou Hai-Shen Wen Yun Li Xin Qi Wen-Juan Li Ya-Xiong Tao |
| author_facet | Kai-Qiang Zhang Zhi-Shuai Hou Hai-Shen Wen Yun Li Xin Qi Wen-Juan Li Ya-Xiong Tao |
| author_sort | Kai-Qiang Zhang |
| collection | DOAJ |
| description | Melanocortin-4 receptor (MC4R) plays important roles in regulation of multiple physiological processes including energy homeostasis, reproduction, sexual function, and other functions in mammals. Recent studies suggested that teleost MC4Rs have different physiological functions and pharmacological characteristics when compared to mammalian MC4Rs. In this study, we investigated spotted sea bass (Lateolabrax maculatus) MC4R (LmMC4R) physiology and pharmacology. Spotted sea bass mc4r consisted of a 984 bp open reading frame encoding a protein of 327 amino acids. LmMC4R was homologous to those of several teleost MC4Rs and human MC4R (hMC4R). qRT-PCR and in situ hybridization revealed that mc4r transcripts were highly expressed in the brain, followed by pituitary and liver. Brain mc4r transcripts were down-regulated in long-term and short-term fasting challenges. LmMC4R was a functional receptor with lower maximal binding and higher basal activity than hMC4R. THIQ was not able to displace 125I-NDP-MSH but could affect intracellular cAMP accumulation, suggesting that it was an allosteric ligand for LmMC4R. In vitro studies with spotted sea bass brain cells indicated that mRNA levels of neuropeptide Y and Agouti-related peptide were down-regulated by α-MSH. In summary, we cloned spotted sea bass MC4R, and showed that it had different pharmacological properties compared to hMC4R, and potentially different functions. |
| first_indexed | 2024-12-20T03:32:24Z |
| format | Article |
| id | doaj.art-273839c6b1284de68aa84892fec23919 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-20T03:32:24Z |
| publishDate | 2019-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-273839c6b1284de68aa84892fec239192022-12-21T19:54:57ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-10-011010.3389/fendo.2019.00705470679Melanocortin-4 Receptor in Spotted Sea Bass, Lateolabrax maculatus: Cloning, Tissue Distribution, Physiology, and PharmacologyKai-Qiang Zhang0Zhi-Shuai Hou1Hai-Shen Wen2Yun Li3Xin Qi4Wen-Juan Li5Ya-Xiong Tao6The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, ChinaDepartment of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, United StatesThe Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, ChinaThe Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, ChinaThe Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, ChinaThe Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, ChinaDepartment of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, United StatesMelanocortin-4 receptor (MC4R) plays important roles in regulation of multiple physiological processes including energy homeostasis, reproduction, sexual function, and other functions in mammals. Recent studies suggested that teleost MC4Rs have different physiological functions and pharmacological characteristics when compared to mammalian MC4Rs. In this study, we investigated spotted sea bass (Lateolabrax maculatus) MC4R (LmMC4R) physiology and pharmacology. Spotted sea bass mc4r consisted of a 984 bp open reading frame encoding a protein of 327 amino acids. LmMC4R was homologous to those of several teleost MC4Rs and human MC4R (hMC4R). qRT-PCR and in situ hybridization revealed that mc4r transcripts were highly expressed in the brain, followed by pituitary and liver. Brain mc4r transcripts were down-regulated in long-term and short-term fasting challenges. LmMC4R was a functional receptor with lower maximal binding and higher basal activity than hMC4R. THIQ was not able to displace 125I-NDP-MSH but could affect intracellular cAMP accumulation, suggesting that it was an allosteric ligand for LmMC4R. In vitro studies with spotted sea bass brain cells indicated that mRNA levels of neuropeptide Y and Agouti-related peptide were down-regulated by α-MSH. In summary, we cloned spotted sea bass MC4R, and showed that it had different pharmacological properties compared to hMC4R, and potentially different functions.https://www.frontiersin.org/article/10.3389/fendo.2019.00705/fullspotted sea bassmelanocortin-4 receptorsignalingallosteric modulatorconstitutive activity |
| spellingShingle | Kai-Qiang Zhang Zhi-Shuai Hou Hai-Shen Wen Yun Li Xin Qi Wen-Juan Li Ya-Xiong Tao Melanocortin-4 Receptor in Spotted Sea Bass, Lateolabrax maculatus: Cloning, Tissue Distribution, Physiology, and Pharmacology Frontiers in Endocrinology spotted sea bass melanocortin-4 receptor signaling allosteric modulator constitutive activity |
| title | Melanocortin-4 Receptor in Spotted Sea Bass, Lateolabrax maculatus: Cloning, Tissue Distribution, Physiology, and Pharmacology |
| title_full | Melanocortin-4 Receptor in Spotted Sea Bass, Lateolabrax maculatus: Cloning, Tissue Distribution, Physiology, and Pharmacology |
| title_fullStr | Melanocortin-4 Receptor in Spotted Sea Bass, Lateolabrax maculatus: Cloning, Tissue Distribution, Physiology, and Pharmacology |
| title_full_unstemmed | Melanocortin-4 Receptor in Spotted Sea Bass, Lateolabrax maculatus: Cloning, Tissue Distribution, Physiology, and Pharmacology |
| title_short | Melanocortin-4 Receptor in Spotted Sea Bass, Lateolabrax maculatus: Cloning, Tissue Distribution, Physiology, and Pharmacology |
| title_sort | melanocortin 4 receptor in spotted sea bass lateolabrax maculatus cloning tissue distribution physiology and pharmacology |
| topic | spotted sea bass melanocortin-4 receptor signaling allosteric modulator constitutive activity |
| url | https://www.frontiersin.org/article/10.3389/fendo.2019.00705/full |
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