The relationships between receptor binding capacity for norepinephrine, angiotensin II, and vasopressin and release of inositol trisphosphate, Ca2+ mobilization, and phosphorylase activation in rat liver

Abstract

Concentration-response relationships for norepinephrine-, angiotensin II-, and vasopressin-stimulated changes in cell Ca2+ content, phosphorylase activation, and cytosolic free Ca2+ and myo-inositol-P3 levels were examined in isolated hepatocytes. The specific binding of radioligands to alpha 1-adrenergic, vasopressin, and angiotensin II receptors was also examined in rat liver plasma membranes. Disparities occurred between the concentration-response curves for myo-inositol-P3 formation and the Ca2+ and phosphorylase responses, with the greatest difference being observed with vasopressin and the smallest with norepinephrine. It was also observed that all three agonists produced the same maximum changes in phosphorylase, cell Ca2+, and cytosolic Ca2+, but the maximum capacity of each agonist to generate myo-inositol-P3 varied greatly and was correlated with the maximum receptor binding capacity. The data indicated that a very small and submaximal elevation of myo-inositol-P3 was sufficient to maximally elevate cytosolic Ca2+ and activate phosphorylase. In addition, the relationship between the accumulation of myo-inositol-P3 and the elevation of cytosolic Ca2+ was similar, irrespective of whether the agonist was norepinephrine, angiotensin II, or vasopressin. It is proposed that the large differences between the concentration-response curves for myo-inositol-P3 formation and Ca2+ and phosphorylase changes observed with vasopressin and angiotensin II are due to the higher density of their receptors on liver cell plasma membranes compared with alpha 1-adrenergic receptors.