Human pheochromocytomas, but not adrenal medulla, express glucagon-receptor gene and possess an in vitro secretory response to glucagon

Glucagon-receptor mRNA was detected by reverse transcription-polymerase cha in reaction in three human pheochromocytomas, but not in four normal adrena l medullas. Quantitative autoradiography demonstrated the presence of abund ant [I-125-Thyr(10)]glucagon binding sites in pheochromocytomas, which were displaced by both cold glucagon and the glucagon receptor antagonist Des-H is(1) [Glu(9)]glucagon amide (GR-A). Adrenal medulla was weakly labeled, an d the binding was not displaced by GR-A. Glucagon enhanced epinephrine and norepinephrine release by pheochromocytoma slices, minimal and maximal effi ctive concentrations being 10(-8) M and 10(-6) hi. Adrenomedullary slices e videnced a weak catecholamine response only to 10(-5) M glucagon. GR-il. ab olished the secretory response to glucagon of pheochromocytomas, but not of adrenal medullas. Collectively, these findings indicate that human pheochr omucytomas, but not adrenal medulla, express glucagon receptors and possess a marked secretory response to glucagon. thereby providing the rationale t o explain the specificity of the glucagon provocative test in the diagnosis of pheochromocytoma. (C) 2001 Elsevier science Inc. All rights reserved.