Molecular and pharmacological characterization of somatostatin receptor subtypes in adrenal, extraadrenal, and malignant pheochromocytomas.

SRIH receptors were quantified by radioautography in 33 pheochromocytomas and 5 normal adrenals. Binding was evenly distributed over the tumors, whereas it was more intense in adrenal medulla than cortex. Binding levels were significantly higher in tumoral than in normal tissue, but did not differ among tumors. At 100 nmol/L, SRIH-14 and octreotide (or BIM23014 in cross-linking experiments to a 57-kilodalton component) comparably displaced SRIH binding, BIM23042 and BIM23052 were less potent, and BIM23056 was inefficient. In increasing doses, the rank order of potency was SRIH-14 > SRIH-28 > octreotide > BIM23052 >> BIM23042 >> > BIM23056. All five species of SRIH receptor (SSTR1-5) messenger ribonucleic acids (mRNAs) were measurable in pheochromocytomas and normal adrenals, SSTR2 and SSTR4 mRNA were the most expressed moieties. The proportion of SSTR5 mRNA species was higher in normal adrenals (21%) than in pheochromocytomas (6%). In the presence of guanylylimidodiphosphate, SRIH binding was reduced by 83%. However, SRIH did not alter basal or forskolin-stimulated adenylyl cyclase activity. Taken together, these pharmacological and molecular data indicate that SRIH binding on pheochromocytomas depends on a mixed population of receptors, mainly of the SSTR2 and SSTR4 subtypes, efficiently coupled to G proteins, but not to adenylyl cyclase inhibition.