NUTRIENT AND PEPTIDE REGULATION OF SOMATOSTATIN-28 SECRETION FROM INTESTINAL CULTURES

Of the two known forms of intestinal somatostatin, somatostatin-28 (S2 8) and S14, S28 predominates in the distal mucosa, whereas S14 is loca lized in the foregut. Although S14 release has been well studied, litt le is known about the factors regulating secretion of S28 from the int estine. Therefore, fetal rat intestinal cultures, which have been prev iously demonstrated to synthesize and secrete predominantly S28, were treated with potential nutrient, neuromodulator/ transmitter, and pept ide secretagogues (n = 4-6/experiment). Oleic acid dose dependently st imulated the release of somatostatin-like immunoreactivity (SLI) to 27 2 +/- 81% of the control value at 1.5 X 10(-4) M (P < 0.01). Gel perme ation analysis (n = 3) demonstrated that this increment was accounted for not only by an increase in the release of S28, but also by an incr ease in that of S14, such that the secretion of both peptides was incr eased in parallel. Of the neuromodulators tested, only the enteric pep tide gastrin-releasing peptide stimulated intestinal SLI secretion, to 386 +/- 60% of the control value at 10(-6) M (P < 0.001); similar to oleic acid, the effects on S28 and S14 were equivalent. Galanin, vasoa ctive intestinal peptide, bethanechol, and epinephrine did not affect SLI release. The duodenal hormone secretin also stimulated SLI release to 310 +/- 78% of the control value at 10(-6) M (P < 0.001); however, secretin caused a preferential release of S14 over that of S28 (S14, 7.8 +/- 2.8-fold; S28, 1.5 +/- 0.1-fold). In contrast, gastrin, cholec ystokinin, glucose-dependent insulinotropic peptide, neurotensin, pept ide YY, epidermal growth factor, and transforming growth factor-alpha had no effect on intestinal SLI release. Thus, luminal nutrients and n euro/endocrine peptides exert differential effects on S28 release from the rat intestine compared with those on S14. These findings implicat e S28 as a distinct regulatory peptide in the physiological setting.