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 chain reaction in three human pheochromocytomas, but not in four normal adrenal medullas. Quantitative autoradiography demonstrated the presence of abundant [I-125-Thyr(10)]glucagon binding sites in pheochromocytomas, which were displaced by both cold glucagon and the glucagon receptor antagonist Des-His(1) [Glu(9)]glucagon amide (GR-A). Adrenal medulla was weakly labeled, and the binding was not displaced by GR-A. Glucagon enhanced epinephrine and norepinephrine release by pheochromocytoma slices, minimal and maximal effictive concentrations being 10(-8) M and 10(-6) hi. Adrenomedullary slices evidenced a weak catecholamine response only to 10(-5) M glucagon. GR-il. abolished the secretory response to glucagon of pheochromocytomas, but not of adrenal medullas. Collectively, these findings indicate that human pheochromucytomas, but not adrenal medulla, express glucagon receptors and possess a marked secretory response to glucagon. thereby providing the rationale to explain the specificity of the glucagon provocative test in the diagnosis of pheochromocytoma. (C) 2001 Elsevier science Inc. All rights reserved.