Naslov
Ligands and Signaling of the G-Protein-Coupled Receptor GPR14, Expressed in Human Kidney Cells

Autori
Lehner, Ulrike ; Velić, Ana ; Schröter, Rita ; Schlatter, Eberhard ; Sinđić, Aleksandra

Izvornik
Cellular physiology and biochemistry (1015-8987) 20 (2007), 1/4; 181-192

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
arachidonic acid; phospholipase A2

Sažetak
Activation of the urotensin II (U-II) receptor, GPR14, leads to an increase in Ca2+, activation of phospholipase A2 (PLA2) and an increase in arachidonic acid. The signaling pathway for guanylin peptides in the kidney involves an unknown G-protein coupled receptor which activates PLA2 and increases arachidonic acid as well. To test if guanylin peptides could be, as U-II, agonists for the GPR14 receptor in the kidney, we used HEK293 and CHO cells transfected with hGPR14 (HEK293+hGPR14, CHO+hGPR14, respectively). Effects of guanylin peptides and U-II were studied by slow-whole-cell patch-clamp analysis and microfluorimetric measurements of intracellular Ca2+. Guanylin peptides and U-II depolarized HEK293+hGPR14 significantly more than wild type cells. These effects were inhibited in the presence of Ba2+ or PLA2 inhibition (AACOCF3), suggesting that guanylin peptides and U-II increase arachidonic acid and inhibit ROMK channels in these cells. However, only U-II was capable to increase the cellular Ca2+, suggesting different mechanism of GPR14 activation by guanylin peptides and U-II. This signaling pathway of U-II involves PKC, because U-II effects in HEK293+hGPR14 cells were inhibited by calphostin C. Guanylin peptides activate PLA2 and inhibit ROMK channels in HEK293 cells transfected with the human GPR14 receptor. Since GPR14 is present in mouse and human CCD it is a candidate for the guanylate cyclase independent receptor for guanylin peptides.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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