Multiple Forms of Immunoreactive Somatostatin: Comparison of Distribution in Neural and Nonneural Tissues and Portal Plasma of the Rat*

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Abstract
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 molecular weight 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 three 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, whereas in the retina and sciatic nerve, about 95% of the IRS was 1.6K SLI. Pancreatic and gastric IRS were also predominantly (∼95%) 1.6K SLI, whereas the gut tissues distal to the stomach contained large quantities of higher molecular weight 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 three 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. It was concluded that 1) there are at least three forms of SLI with molecular weights of 14,000, 3,000, and 1,600 daltons which are likely to represent single chain polypeptides; 2) the relative amounts of the three forms of SLI vary considerably in different tissues, suggesting basic differences in the intracellular processing of the two high molecular weight SLIs in different tissues; 3) no distinction between neural and nonneural somatostatin cells can be made on the basis of the intracellular distribution of the three molecular forms; 4) 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; and 5) all three tissue forms of SLI appear to be secreted.