Summary: | <p>Abstract</p> <p>Background</p> <p>Previous studies have shown that several agents that stimulate heptahelical G-protein coupled receptors activate the extracellular signal regulated kinases ERK1 (p44<sup>mapk</sup>) and ERK2 (p42<sup>mapk</sup>) in hepatocytes. The molecular pathways that convey their signals to ERK1/2 are only partially clarified. In the present study we have explored the role of Ca<sup>2+</sup> and Ca<sup>2+</sup>-dependent steps leading to ERK1/2 activation induced by norepinephrine and prostaglandin (PG)F<sub>2α</sub>.</p> <p>Results</p> <p>Pretreatment of the cells with the Ca<sup>2+</sup> chelators BAPTA-AM or EGTA, as well as the Ca<sup>2+</sup> influx inhibitor gadolinium, resulted in a partial decrease of the ERK response. Furthermore, the calmodulin antagonists W-7, trifluoperazine, and J-8 markedly decreased ERK activation. Pretreatment with KN-93, an inhibitor of the multifunctional Ca<sup>2+</sup>/calmodulin-dependent protein kinase, had no effect on ERK activation. The Src kinase inhibitors PP1 and PP2 partially diminished the ERK responses elicited by both norepinephrine and PGF<sub>2α</sub>.</p> <p>Conclusion</p> <p>The present data indicate that Ca<sup>2+</sup> is involved in ERK activation induced by hormones acting on G protein-coupled receptors in hepatocytes, and suggest that calmodulin and Src kinases might play a role in these signaling pathways.</p>
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