The calcium-sensing receptor stimulates JNK in MDCK cells

The calcium-sensing receptor (CaR) stimulates ERK1 in rat fibroblasts, but its effect on other MAP kinases is not known. We used a model of renal dist al tubule, the MDCK cell, to determine the effects of Call. stimulation on Jun kinase (JNK) activity. Stimulation of the Call with 5 mM Ca2+ resulted in a time-dependent increase in JNK activity. Activation of JNK occurred pr eferentially with stimulation on the basal surface relative to the apical s urface. Basal administration of the CaR agonist gadolinium (30 mu m) also s timulated JNK activity. Pertussis toxin blocked the ability of both CaR ago nists to stimulate JNK, indicating that the effect was mediated through G(i alpha) class G proteins. Finally, we used confocal microscopy to determine that the CaR was located predominantly on the basal surface. These studies demonstrate for the first time that the CaR stimulates JNK activity. (C) 2 000 Academic Press.