Regulation of intestinal proglucagon-derived peptide secretion by intestinal regulatory peptides.
The physiological regulation of intestinal proglucagon-derived peptide secretion has not been well studied. We have therefore used a fetal rat intestinal cell culture model to investigate the control of secretion of the gut glucagon-like immunoreactive (GLI) peptides by other intestinal regulatory peptides in vitro. Secretion of the intestinal GLI peptides was found to be stimulated in a dose-dependent fashion by the intestinal endocrine peptide, gastric inhibitory peptide (at greater than or equal to 10(-10) M, P less than 0.05), and by the neurocrine peptides, gastrin-releasing peptide (at greater than or equal to 10(-12) M, P less than 0.05), and calcitonin gene-related peptide (at greater than or equal to 10(-8) M, P less than 0.05). Gastrin-releasing peptide and its amphibian equivalent, bombesin were equipotent in stimulating GLI peptide secretion. In contrast, the endocrine and neurocrine intestinal somatostatin-related peptides, somatostatin-28 and -14, inhibited release of the GLI peptides, at concentrations of 10(-10) (P less than 0.01) and 10(-8) (P less than 0.01) M, respectively, with significant differences in potency between the two peptides detected at 10(-10) M (P less than 0.05). The inhibitory effects of both somatostatin-28 and -14 could be blocked by preincubation of the cells with pertussis toxin (P less than 0.05). Dose-dependent stimulation of gut GLI peptide secretion was also detected in response to treatment of cultured cells with sodium oleate (at 10(-4) M; P less than 0.05), or with the cholinergic agonist bethanecol (at greater than or equal to 100 microM; P less than 0.05). Other endocrine [cholecystokinin, glucagon, glucagon-like peptide-1(1-37), glucagon-like peptide-1(7-37), glucagon-like peptide-2, neurotensin, and peptide YY] and neurocrine (vasoactive intestinal peptide) peptides, and the synthetic glucocorticoid, dexamethasone, were without effect on secretion of the gut GLI peptides, at doses of 10(-12) to 10(-6) M. The results of the present study therefore demonstrate that secretion of the intestinal proglucagon-derived peptides is under the regulatory control of a wide variety of intestinal endocrine and neurocrine peptides, as well as nutrients (fats) and neurotransmitters (acetylcholine).
Department of Physiology, University of Toronto, Ontario, Canada.
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Brubaker
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D004702:Endocrine Glands / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism* / Q000502:physiology; D052336:Proglucagon; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats
D005938:Glucocorticoids; D018377:Neurotransmitter Agents; D010455:Peptides; D011498:Protein Precursors; D052336:Proglucagon; D005934:Glucagon