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Advances in Pharmacological Sciences
Volume 2010, Article ID 269274, 8 pages
Research Article

Mechanism of Cytosolic Phospholipase A 2 Activation in Ghrelin Protection of Salivary Gland Acinar Cells against Ethanol Cytotoxicity

Research Center, University of Medicine and Dentistry of New Jersey, 110 Bergen Street, P.O. Box 1709, Newark, NJ 07103 - 2400, USA

Received 4 March 2010; Accepted 19 April 2010

Academic Editor: C. H. Cho

Copyright © 2010 Bronislaw L. Slomiany and Amalia Slomiany. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Ghrelin, a peptide hormone, newly identified in oral mucosal tissues, has emerged recently as an important mediator of the processes of mucosal defense. Here, we report on the mechanism of ghrelin protection against ethanol cytotoxicity in rat sublingual salivary gland cells. The protective effect of ghrelin was associated with the increase in NO and PGE2, and upregulation in cytosolic phospholipase A 2 ( c P L A 2 ) activity and arachidonic acid (AA) release. The loss in countering effect of ghrelin occurred with cNOS inhibitor, L-NAME, as well as indomethacin and COX-1 inhibitor, SC-560, while COX-2 inhibitor, NS-398, and iNOS inhibitor, 1400W, had no effect. The effect of L-NAME was reflected in the inhibition of ghrelin-induced cell capacity for NO production, c P L A 2 activation and PGE2 generation, whereas indomethacin caused only the inhibition in PGE2. Moreover, the ghrelin-induced up-regulation in AA release was reflected in the c P L A 2 phosphorylation and S-nitrosylation. Inhibition in ghrelin-induced S-nitrosylation was attained with L-NAME, whereas the ERK inhibitor, PD98059, caused the blockage in c P L A 2 protein phosphorylation as well as S-nitrosylation. Thus, ghrelin protection of salivary gland cells against ethanol involves cNOS-derived NO induction of c P L A 2 activation through S-nitrosylation for the increase in AA release at the site of COX-1 action for PGE2 synthesis.