Orphan GPCR receptors

Strategies for Ligand identification for Orphan GPCR Receptors... 

Orphan G protein-coupled receptors Orphan GPCRs Orphan seipentine receptors Orphan nuclear receptor... 

H4 receptors are very similar to H3 receptors in gene structure and signal transduction, but show limited expression in the brain. The H4 receptor gene was identified in 2000 as a direct consequence of the human genome project. Use of the human H3 receptor sequence led to the identification of a related orphan GPCR. 

Melatonin is an indole-derived anterior pituitary hormone that causes downstream inhibition of a-MSH-induced melanogenesis. Melatonin is antiamnesic, synchronizes circadian and circannual rhythms and is metabolized to 5-methoxytryptamine. Melatonin acts via GPCRs MT1 and MT2 (which both couple through Gai and cAMP decrease). MT1 may also couple via Gao and Gaq to activate PLC (and hence increase cytosolic Ca2+) and via G Gy activation of PLA2. Melatonin can further interact with nuclear receptor superfamily orphan retinoid receptors RZR/ROR. Melatonin fluctuates with a circadian rhythm and is elevated in blood during the night. Melatonin is accordingly of social importance in relation to shift work and jet-lag. Melatonin and 5-methoxytryptamine occur in some plants (Table 5.8). 

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