High biological activity of the synthetic replicates of somatostatin-28 and somatostatin-25.

We have isolated form extracts of ovine hypothalami two molecules characterized as somatostatin-28 and somatostatin-4-28 (referred to as somatostatin-25). They were reproduced by solid hase synthesis. In equimolar ratio and depending upon the experimental conditions, synthetic somatostatin-28 ans somatostatin-25 are 3-14 times more potent than somatostatin-14 to inhibit the basal in vitro secretion of growth hormone or as stimulated by prostaglandin (PGE2). In early studies in vivo, somatostatin-28 and somatostatin-25 are also more potent than somatostatin-14 in inhibiting the secretion of growth hormone acutely stimulated in the rat by injection of morphine; somatostatin-28 is also longer-acting than somatostatin-14. These results suggest that somatostatin-14, as originally isolated, is a biologically active fragment of a larger molecule of greater specific activity; it should be considered as another form of somatostatin with high biological activity present in some tissues and likely secreted y the tissues along with somatostatin-14 and possibly other somatostatin-peptides of diverse sizes.