Nutrient and peptide regulation of somatostatin-28 secretion from intestinal cultures.
Of the two known forms of intestinal somatostatin, somatostatin-28 (S28) and S14, S28 predominates in the distal mucosa, whereas S14 is localized in the foregut. Although S14 release has been well studied, little is known about the factors regulating secretion of S28 from the intestine. Therefore, fetal rat intestinal cultures, which have been previously demonstrated to synthesize and secrete predominantly S28, were treated with potential nutrient, neuromodulator/transmitter, and peptide secretagogues (n = 4-6/experiment). Oleic acid dose dependently stimulated the release of somatostatin-like immunoreactivity (SLI) to 272 +/- 81% of the control value at 1.5 x 10(-4) M (P < 0.01). Gel permeation analysis (n = 3) demonstrated that this increment was accounted for not only by an increase in the release of S28, but also by an increase in that of S14, such that the secretion of both peptides was increased in parallel. Of the neuromodulators tested, only the enteric peptide 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, vasoactive 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, cholecystokinin, glucose-dependent insulinotropic peptide, neurotensin, peptide YY, epidermal growth factor, and transforming growth factor-alpha had no effect on intestinal SLI release. Thus, luminal nutrients and neuro/endocrine peptides exert differential effects on S28 release from the rat intestine compared with those on S14. These findings implicate S28 as a distinct regulatory peptide in the physiological setting.
Brubaker
P L
PL
Department of Physiology, University of Toronto, Ontario, Canada. p.brubaker@utoronto.ca
Gronau
K A
KA
Asa
S L
SL
Greenberg
G R
GR
D000818:Animals; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D019886:Gastrin-Releasing Peptide / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D019301:Oleic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000378:metabolism*; D053561:Somatostatin-28
D019301:Oleic Acid; C013173:osteum; D013004:Somatostatin; D053561:Somatostatin-28; D019886:Gastrin-Releasing Peptide; D002766:Cholecystokinin; D004837:Epinephrine