Repetitive transient rises in cytoplasmic free calcium in hormone-stimulated hepatocytes

Abstract

In the stressed animal, the vasoactive hormones vasopressin and angiotensin-II and the neurotransmitter noradrenaline induce liver cells to release glucose from glycogen. The intracellular signal that links the cell-surface receptors for noradrenaline (α₁) and vasoactive peptides to activation of glycogenolysis is known to be a rise in the cytoplasmic concentration of free calcium ions (free Ca)^1–3. The receptors for these agonists induce the hydrolysis of phosphatidylinositol 4,5-bisphosphate, a minor plasmalemma lipid, to produce inositol trisphosphate and diacylglycerol^3–5. Inositol trisphosphate has been shown to mobilize intracellular calcium in hepatocytes^3,6–8. We show here, by means of aequorin measurements in single, isolated rat hepatocytes, that the free Ca response to these agonists consists of a series of transients. Each transient rose within 3 s to a peak free Ca of at least 600 nM and had a duration of approximately 7 s. The transients were repeated at intervals of 0.3–4 min, depending on agonist concentration. Between transients, free Ca returned to the resting level of ˜200nM. Clearly, the mechanisms controlling free Ca in hepatocytes are more complex than hitherto suspected.