Gastric inhibitory peptide (GIP), pancreatic glucagon and vasoactive intestinal peptide (VIP) are cAMP-inducing hormones in the human gastric cancer cell line HGT-1. Homologous desensitization of VIP receptor activity.
GIP (EC50 = 8 X 10(-9) M, 5-fold stimulation), pancreatic glucagon (EC50 = 10(-8)M, 13-fold) and porcine or chicken VIP (EC50 = 2.5 X 10(-9) M, 10-fold) are shown to activate the cAMP generating system in HGT -1 cells. Combinations of GIP, pancreatic glucagon and VIP indicate the occurrence of 3 separate sets of recognitions sites for these 3 peptides. Accordingly, chronic treatment of cultured HGT -1 cells by VIP (10(-8) M) during 6 days resulted in homologous desensitization of VIP receptor activity. Other peptides structurally related to the secretin-glucagon family, to neurotensin, or to gastrin are either ineffective or very weak agonist (hpGRF). GIP or pancreatic glucagon are inactive on the human colonic cell line HT-29, indicating the gastric specificity of the effect of GIP and glucagon in transformed epithelial cells originating from the human gastrointestinal tract. This implies that GIP and (pancreatic-entero) glucagon peptides may regulate gastric secretions directly, under similar mechanisms that those we evidenced in the rat.
D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D018005:Receptors, Vasoactive Intestinal Peptide; D013274:Stomach Neoplasms / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D005768:Gastrointestinal Hormones; D011956:Receptors, Cell Surface; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D005749:Gastric Inhibitory Polypeptide; D005934:Glucagon; D000242:Cyclic AMP