Identification of inositol 1,4,5-trisphosphate binding in human pheochromocytoma

An attempt was made to identify a specific binding of inositol 1,4,5-trisphosphate (IP3) to human chromaffin cell tumors. Crude microsomal fractions of pheochromocytomas possessed significant binding sites for [3H]IP3 with high- and low-affinity constants (Kd = 5.46 and 538 nM, respectively). The binding to these sites was rapid, saturable (reached equilibrium by 1 min at 0 degrees C) and reversible. Competition studies with other inositol phosphate analogs indicated the stereotypic specific binding for IP3. Although no significant difference was observed in the binding densities of IP3 between pheochromocytomas and adrenal nonfunctioning adenomas, the values of high-affinity constants were significantly lower in the former than the latter group (5.77 +/- 1.07, n = 5 vs. 11.30 +/- 1.98 nM, n = 4, p less than 0.05). The present data indicate that characteristics of IP3 binding sites are congruous with their receptor functions and that changes in its binding sites may contribute to the biochemical dissimilitudes in pheochromocytomas.