Concomitant Expression of Endothelin Receptor Subtype and Isopeptide by Pheochromocytoma and Bovine Adrenal Medulla.

Abstract

Endothelin (ET) isopeptide and receptor subtype are distributed in various tissues, suggesting diverse functions as local factors other than acting as potent vasoconstrictors. We have studied whether ET Isopeptide and receptor subtype are concomitantly expressed in pheochromocytoma and bovine adrenal medulla by binding studies and Northern blot analysis and compared the results with those in human and bovine adrenal cortex. Binding studies using [125I]ET-1 as a radioligand revealed a single class of high-affinity binding sites for ET-1 in membranes from two pheochromocytomas and normal bovine adrenal medulla, which were almost comparable to those from human and bovine adrenal cortex. ET-1 and ET-2 equipotently and competitively inhibited [125I]ET-1 binding to the membranes, whereas ET-3 was far less potent than ET-1 at higher concentrations, suggesting heterogeneous subpopulations of ET receptors. Northern blot analysis using cDNAs for ETA and ETB receptors revealed that both ETA and ETB receptor mRNAs are expressed in pheochromocytoma and bovine adrenal medulla in a similar fashion as in human and bovine adrenal cortex. Northern blot analysis using cDNAs for human preproET-1 and preproET-3 as probes also revealed the concomitant expression of preproET-1 mRNA in pheochromocytoma and bovine adrenal medulla and preproET-3 mRNA in human adrenal cortex. These data demonstrate for the first time that ET receptor subtype (ETA and ETB) and ET isopeptide (ET-1 and ET-3) are concomitantly expressed by pheochromocytoma as well as bovine adrenal medulla, suggesting the paracrine/autocrine function of ET in adrenomedullary chromaffin cells. (Hypertens Res 1993;16: 215-219)