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Cloning and molecular characterization of the novel human melanin-concentrating hormone receptor MCH2.
- Source :
-
Molecular pharmacology [Mol Pharmacol] 2001 Oct; Vol. 60 (4), pp. 632-9. - Publication Year :
- 2001
-
Abstract
- Using a genomics-based approach for screening orphan G-protein-coupled receptors, we have identified and cloned a novel high-affinity, melanin-concentrating hormone (MCH) receptor. This receptor, named S643b, displays the greatest overall identity (32%) with the previously reported human SLC-1 receptor (MCH1) and to a lesser extent with the somatostatin receptor subtypes. The gene encoding the S643b receptor spans more than 23 kilobase pairs (kb) and was mapped, by radiation hybrid experiments, on chromosome 6q14.3-q15. Comparison of the S643b cDNA with human genomic sequence reveals that the 340-amino-acid receptor is encoded by five exons. Its tissue distribution, as determined by Northern blot and reverse transcription-polymerase chain reaction analysis, indicates that a 4-kb transcript is predominantly expressed in the brain. When expressed in Chinese hamster ovary (CHO) cells, the S643b receptor displays a strong, dose-dependent, transient elevation of intracellular calcium in response to MCH (EC(50) = 9.5 nM). During the present study, we isolated a splice variant, designated S643a, encoding for a receptor that was not activated by MCH in a cellular calcium mobilization assay. Comparative pharmacological studies using CHO cells stably expressing either SLC-1 or S643b receptors demonstrated that similar structural features of MCH are required to stimulate intracellular Ca(2+) mobilization at both receptors. The identification and localization of this new MCH receptor (MCH2) provides further insight into the physiological implication of MCH in modulating behavioral responses, including food intake.
- Subjects :
- Amino Acid Sequence
Base Sequence
Chromosome Mapping
Cloning, Molecular
DNA, Complementary analysis
Humans
Molecular Sequence Data
Peptides pharmacology
RNA, Messenger metabolism
Receptors, G-Protein-Coupled
Receptors, Pituitary Hormone metabolism
Receptors, Somatostatin chemistry
Sequence Homology, Amino Acid
Tissue Distribution
Chromosomes, Human, Pair 6
Receptors, Pituitary Hormone genetics
Receptors, Somatostatin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0026-895X
- Volume :
- 60
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Molecular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 11562423