Characterization of a somatostatin-28 containing the (Tyr-7, Gly-10) derivative of somatostatin-14: a terminal active product of prosomatostatin II processing in anglerfish pancreatic islets

Abstract

Anglerfish (Lophius piscatorius) Brockmann organs contain a form of somatostatin-14, identical to the hypothalamic tetradecapeptide, and two distinct forms of somatostatin-28, which can be separated by reversed-phase high-pressure liquid chromatography (HPLC). Analysis of the NH2-terminal amino acid sequence and comparison of the ability to incorporate 125I indicate that one of these forms corresponds to an octacosapeptide including in its sequence the (Tyr-7, Gly-10) derivative of somatostatin-14 (somatostatin II). Exposure of this somatostatin-28 species to an endopeptidase activity from the rat brain cortex generates a peptide immunologically related to somatostatin and undistinguishable from synthetic (Tyr-7, Gly-10) somatostatin-14 II by HPLC. This somatostatin-28 II exhibits a potent inhibitory effect on growth hormone release by rat anterior pituitary cells, comparable to the other somatostatin-28 form. Since (Tyr-7, Gly-10) somatostatin-14 II cannot be detected in anglerfish pancreatic islets, these results indicate that somatostatin-28 II represents the terminal active product of prosomatostatin II processing, whose structure was predicted from the cDNA nucleotide sequence corresponding to the second mRNA cloned from anglerfish Brockmann organs [Hobart, P., Crawford, R., Shen, L. P., Pictet, R. & Rutter, W. J. (1980) Nature (London) 288, 137-141].