OCCURRENCE OF 2 SOMATOSTATIN VARIANTS IN THE FROG BRAIN - CHARACTERIZATION OF THE CDNAS, DISTRIBUTION OF THE MESSENGER-RNAS, AND RECEPTOR-BINDING AFFINITIES OF THE PEPTIDES

In tetrapods, only one gene encoding a somatostatin precursor has been identified so far, The present study reports the characterization of the cDNA clones that encode two distinct somatostatin precursors in th e brain of the frog Rana ridibunda, The cDNAs were isolated by using d egenerate oligonucleotides based on the sequence of the central region of somatostatin to screen a frog brain cDNA library, One of the cDNAs encodes a 115-amino acid protein (prepro-somatostatin-14; PSS1) that exhibits a high degree of structural similarity with the mammalian som atostatin precursor, The other cDNA encodes a 103-amino acid protein ( prepro-[Pro(2), Met(13)] somatostatin-14; PSS2) that contains the sequ ence of the somatostatin analog (peptide SS2) at its C terminus, but d oes not exhibit appreciable sequence similarity with PSS1 in the remai ning region, In situ hybridization studies indicate differential expre ssion of the PSS1 and PSS2 genes in the septum, the lateral part of th e pallium, the amygdaloid complex, the posterior nuclei of the thalamu s, the ventral hypothalamic nucleus, the torus semicircularis and the optic tectum, The somatostatin variant SS2 was significantly more pote nt (4-6 fold) than somatostatin itself in displacing [I-125-Tyr(0), D- Trp(8)] somatostatin-14 from its spe cific binding sites, The present study indicates that the two somatostatin variants could exert differe nt functions in the frog brain and pituitary. These data also suggest that distinct genes encoding somatostatin variants may be expressed in the brain of other tetrapods.