INOSITOL-PHOSPHOGLYCAN INHIBITS CALCIUM OSCILLATIONS IN HEPATOCYTES BY REDUCING CALCIUM-ENTRY

Inositol-phosphoglycan (IPG) is a putative mediator of insulin action that has been shown to affect numerous biochemical processes. IPG, pre pared from liver membranes, promptly inhibited phenylephrine- or vasop ressin-induced [Ca2+](i) oscillations when perfused over Fura-2-dextra n injected rat hepatocytes. An antibody to IPG suppressed the inhibito ry effect of insulin on the [Ca2+](i) oscillations. Measurement of the rate of quench of cytoplasmic Fura-2 by extracellular Mn2+ showed tha t Ca2+ entry occurred continuously in the unstimulated cell and was no t affected by phenylephrine or vasopressin. IPG, specifically, almost completely abolished the Mn2+ quench rate. Elevated extracellular [Ca2 +] reversed the inhibitory effect of IPG on [Ca2+](i) oscillations. We conclude that IPG inhibits the hepatocyte Ca2+ oscillator by reducing the continuous Ca2+ influx that is required to sustain oscillations i n [Ca2+](i).