Circadian Pacemaker

Figure 1

constant dark (source)

In my previous blog post, I mentioned that the GHSR1 ghrelin receptor has a high level of activity independent of ghrelin binding.  Recently, an “orphan” G Protein-coupled Receptor (GPCR) (Gpr176) has been implicated in the function of the circadian pacemaker of the suprachiasmatic nucleus (SCN). Gpr176 might not have a ligand and it might function simply by having daily swings in the level of its expression.

staining for Gpr176 in the SCN

Gpr176 in the SCN (source)

In gene knock-out mice without this particular GPCR (Gpr176-/-) the circadian period is slower than in normal mice. This function of Gpr176 was discovered by searching through the many (about 140) orphan GPCRs for those that have high levels of expression in the suprachiasmatic nucleus. Gpr176 expression was shown to be regulated with a circadian pattern.


circadian expression of Gpr176 mRNA [cry1] (source)

It was previously known that vasoactive intestinal peptide (VIP) regulates the circadian rhythm.

The Vipr2 GPCR for VIP stimulates adenylate cyclase and  increased levels of cAMP in neurons of the SCN circadian pacemaker. Gpr176 inhibits adenylate cyclase through the inhibitory G-protein, Gz.

cAMP levels

High cAMP in Gpr176 knockout mice (source)

In gene knockout mice that do not express Gpr176, the measured levels of cAMP in the SCN are higher than for control mice.



About johnwschmidt

Exploring medical physiology.
This entry was posted in brain, circadian rhythm, signal transduction. Bookmark the permalink.

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