PT  - JOURNAL ARTICLE
AU  - M. Rodriguez
AU  - P. Beauverger
AU  - I. Naime
AU  - H. Rique
AU  - C. Ouvry
AU  - S. Souchaud
AU  - S. Dromaint
AU  - N. Nagel
AU  - T. Suply
AU  - V. Audinot
AU  - J. A. Boutin
AU  - J. P. Galizzi
TI  - Cloning and Molecular Characterization of the Novel Human Melanin-Concentrating Hormone Receptor MCH2
DP  - 2001 Oct 01
TA  - Molecular Pharmacology
PG  - 632--639
VI  - 60
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/60/4/632.short
4100  - http://molpharm.aspetjournals.org/content/60/4/632.full
SO  - Mol Pharmacol2001 Oct 01; 60
AB  - 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 (EC50 = 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 Ca2+ 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. The American Society for Pharmacology and Experimental Therapeutics