ENDOTHELIN-STIMULATED CAPACITATIVE CALCIUM-ENTRY IN ENTERIC GLIAL-CELLS - SYNERGISTIC EFFECTS OF PROTEIN-KINASE-C ACTIVITY AND NITRIC-OXIDE

Depletion of intracellular calcium stores by agonist stimulation is co upled to calcium influx across the plasma membrane, a process termed c apacitative calcium entry. Capacitative calcium entry was examined in cultured guinea pig enteric glial cells exposed to endothelin 3. Endot helin 3 (10 nM) caused mobilization of intracellular calcium stores fo llowed by influx of extracellular calcium, This capacitative calcium i nflux was inhibited by Ni2+ (89 +/- 2%) and by La3+ (78 +/- 2%) but wa s not affected by L-, N-, or P-type calcium channel blockers. Cheleryt hrine, a specific antagonist of protein kinase C, dose-dependently inh ibited capacitative calcium entry. The nitric oxide synthase inhibitor N-G-nitro-L-arginine decreased calcium influx in a dose-dependent man ner. The combination of chelerythrine and N-G-nitro-L-arginine produce d synergistic inhibitory effects, Capacitative calcium entry occurs in enteric glial cells via anthanum-inhibitable channels through a proce ss regulated by protein kinase C and nitric oxide.