Receptors and Signal Transduction

The neuropeptide MCH acts via a unique receptor, which has been recently identified. The receptor is an orphan G protein-coupled receptor (SLC-1) which binds MCH with nanomolar affinity. The receptor has the typical seven transmembrane domains of G protein-coupled receptors. The MCH receptor of rats and humans shares significant homology and, in addition, reveals homology with the somatostatin receptor.

The distribution of SLC-1 mRNA and its corresponding protein have been examined by in situ hybridization and immunocytochemistry.

SLC-1 mRNA and SLC-1 protein are widely expressed throughout the brain. Strong immunoreactivity is observed in areas that overlap extensively with regions mapping positive for mRNA. SLC-1 signals are observed in the cerebral cortex, the olfactory tubercle, the hippocampal formation, the caudate-putamen, the nucleus accumbens, the thalamus and the hypothalamus (ventromedial and dorsomedial nuclei of the hypothalamus) as well as in various nuclei of the mesencephalon and rhombencephalon.

Interestingly, the MCH receptor has also been observed in areas associated with the dopaminergic system, such as the substantia nigra and the ventral teg-mental area.

The binding of MCH to its receptor induces calcium mobilization and can inhibit the forskolin-induced accumulation of cAMP.

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