The constitutive activity of the ghrelin receptor attenuates apoptosis via a protein kinase C-dependent pathway

The ghrelin receptor (GHS-R1a) displays a high level of constitutive signaling through a phospholipase C/protein kinase C-dependent pathway. Therefore, we have investigated the role of agonist-dependent and agonist-independent signaling of GHS-R1a in apoptosis using the seabream GHS-R1a stably expressed in human embryonic kidney 293 cells (HEK-sbGHS-R1 a cells). Cadmium-induced activation of caspase-3 was significantly attenuated in HEK-sbGHS-R1 a cells compared to wild-type HEK293 cells, while the apoptotic responses to the protein kinase C inhibitor staurosporine were similar. GHS-R1a ligands had no effect on caspase-3 activation or on cell proliferation. Concentrations of the inverse agonist [D-Arg(1),DPhe(5),D-Trp(7),(9),Leu(11)]-substance P sufficient to inhibit constitutive inositol phosphate generation did not enhance caspase-3 activity, suggesting a possible role of phosphatidylcholine-specific phospholipase C in the anti-apoptotic activity of GHS-R1 a. In conclusion, our data suggests that the constitutive activity of sbGHS-R1 a may be sufficient alone to attenuate apoptosis via a protein kinase C-dependent pathway. (c) 2008 Elsevier Ireland Ltd. All rights reserved.