SOMATOSTATIN EXPRESSION IN HUMAN RENAL-CORTEX AND MESANGIAL CELLS

Somatostatin modulates important physiologic functions of the kidney, including mesangial cell contraction, glomerular prostaglandin synthes is, and phosphate, water and sodium excretion. In diabetic nephropathy , somatostatin inhibits renal hypertrophy. High affinity somatostatin receptors are expressed in the kidney. Circulating somatostatin concen trations, however, are generally well below the affinity constants of known somatostatin receptors. Thus, we hypothesized that somatostatin is produced in the kidney and released locally to act in an autocrine/ paracrine manner. Using reverse transcriptase and polymerase chain rea ction (RT-PCR) analysis, we found that fresh human renal cortex and cu ltured human mesangial cells express somatostatin mRNA. Restriction en zyme and Southern blot analysis confirmed that RT-PCR cDNA products we re derived from somatostatin mRNA. Radioimmunoassay of mesangial cell culture supernatants demonstrated SS-immunoreactive peptide (87+/-30 p g/ml compared to 19+/-9 pg/ml in medium not exposed to cells; P < 0.05 ). In contrast, renal cells did not transcribe detectable levels of va soactive intestinal peptide (VIP) or neuropeptide Y (NPY) mRNA, nor di d they synthesize measurable peptide. Our results demonstrate that ren al cells produce somatostatin and suggest that kidney-derived somatost atin may regulate renal function in an autocrine/paracrine manner. Cha racterization of this pathway may lead to novel methods to alter the c ourse of diabetic nephropathy and other renal diseases. (C) 1997 Elsev ier Science B.V.