| 研究実績の概要 |
Prrt3 is an orphan metabotropic receptor of family C GPCR and there is no publication concerning Prrt3. We have observed that Prrt3 is highly expressed in mouse brain. Since the physiological roles of Prrt3 are still unknown, we aim to identify the endogenous ligands of Prrt3 and elucidate the roles of Prrt3 in the central nervous system (CNS).We have performed behavioral analyses using homozygous Prrt3 knockout (KO) mice and electrophysiological experiments using Xenopus oocytes, and we observed the following results:
(1) We created homozygous Prrt3 KO mice and performed behavioral analyses. By the Barnes probe test to analyze the spatial memory, we observed a significant decrease in the retention of spatial memory after 4 weeks interval from the completion of training. The scores of homo Prrt3 KO mice of Latency to the 1st arrival at the target hole, Error to 1st and Distance to 1st were all significantly higher than those of control mice.
(2) By monitoring GIRK currents, we screened several types of small-molecule libraries and observed that some muscarinic receptor agonists, but not ACh, slightly activates the Prrt3. We also happened to identify several novel inhibitors of GIRK channel, such as antihistamine drugs. We clarified the inhibition mechanisms of GIRK channel by these drugs and published the data and results in British Journal of Pharmacology. These results provide us with clues toward the understanding of physiological roles of Prrt3.
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