MULTIPLE FORMS OF IMMUNOREACTIVE SOMATOSTATIN - COMPARISON OF DISTRIBUTION IN NEURAL AND NON-NEURAL TISSUES AND PORTAL PLASMA OF THE RAT

The present study was undertaken to partly characterize and compare the relative amounts of the different molecular forms of somatostatin in the major somatostatin-containing tissues and portal plasma of the rat. Immunoreactive somatostatin (IRS) was extracted from hypothalamus, cerebral cortex, neural retina, sciatic nerve, pancreas, stomach, duodenum, jejunum, ileum, colon and portal venous plasma and fractionated on Sephadex G-50 columns equilibrated with 6 M urea. Three peaks with somatostatin-like immunoreactivity (SLI) were identified. Peak I had an apparent MW of 14,000 daltons, (14K SLI), peak II coeluted with synthetic somatostatin-28 (3K SLI), and peak III coeluted with SRIF (1.6K SLI). The relative proportions of the 3 molecular forms were unchanged after treatment with 8 M guanidine hydrochloride and thioglycol and varied considerably from tissue to tissue. In the hypothalamus and cerebral cortex, approximately 70% of the IRS was present as 1.6K SLI, 25% as 3K SLI, and 5% as 14K SLI; in the retina and sciatic nerve, about 95% of the IRS was 1.6K SLI. Pancreatic and gastric IRS were also predominantly (.apprx. 95%) 1.6K SLI; the gut tissues distal to the stomach contained large quantities of higher MW SLI, especially 3K SLI. Separate analysis of the mucosal and muscle layers of the jejunum, ileum and colon revealed 3K SLI as the main molecular species in the mucosa (55-73% of total IRS) and 1.6K SLI as the main type in the muscle (70-95% of total IRS). All 3 forms of SLI were found in the portal vein in amounts that correlated with the total content of 14K SLI, 3K SLI and 1.6K SLI in the entire gut and pancreas. There are at least 3 forms of SLI with MW of 14,000, 3000 and 1600 daltons which are likely to represent single chain polypeptides. The relative amounts of the 3 forms of SLI vary considerably in different tissues, suggesting basic differences in the intracellular processing of the 2 high-MW SLI in different tissues. No distinction between neural and nonneural somatostatin cells can be made on the basis of the intracellular distribution of the 3 molecular forms. The finding of 3K SLI (somatostatin-28 equivalent) as the main molecular species in intestinal mucosa together with the reported high biological activity of somatostatin-28 suggest independent physiological functions for this molecule; all 3 tissue forms of SLI appear to be secreted.