Pancreastatin: a novel peptide inhibitor of parietal cell secretion.
Pancreastatin is a recently identified 49-amino-acid peptide found in gastrointestinal tract and gastric mucosa. Its biologic effects on gastric function are unknown. The aim of this study was to determine the effects of pancreastatin [33-49] (the synthetic C-terminal fragment) on acid secretion and somatostatin release in vitro. Isolated rabbit gastric glands were prepared by means of collagenase digestion. Acid secretion was assessed indirectly with use of 14C-aminopyrine (AP) uptake by glands, and somatostatin release from D cells was measured with radioimmunoassay. Pancreastatin alone (10(-10) to 10(-6) mol/L) had no effect on 14C-AP uptake compared with unstimulated glands. In contrast, pancreastatin inhibited with histamine-(10(-6), 10(-5) mol/L; p less than 0.005) and carbachol-(10(-5), 10(-4) mol/L; p less than 0.001) stimulated 14C-AP uptake in a dose-dependent manner. Neither forskolin-(10(-6), 10(-4) mol/L; p greater than 0.50) or 8-Br-cAMP-(10(-5), 10(-4) mol/L; p greater than 0.30) stimulated 14C-AP uptake were influenced by pancreastatin. Pancreastatin had no effect on somatostatin release from glands. These data suggest that pancreastatin probably acts at receptor or membrane level, inhibiting both histamine- and carbachol-stimulated 14C-AP uptake. These effects are not mediated by D cell somatostatin release. It is possible that pancreastatin acts as a paracrine or endocrine inhibitory regulator of parietal cell secretion.
Lewis
J J
JJ
Gastrointestinal Surgical Research Group, Yale University School of Medicine, West Haven, Conn.
Zdon
M J
MJ
Adrian
T E
TE
Modlin
I M
IM
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D053379:Chromogranin A; D005576:Colforsin / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D010187:Pancreatic Hormones / Q000494:pharmacology*; D010295:Parietal Cells, Gastric / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D011817:Rabbits; D013004:Somatostatin / Q000378:metabolism
D053379:Chromogranin A; D010187:Pancreatic Hormones; D010455:Peptides; D000632:Aminopyrine; C050836:pancreastatin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013004:Somatostatin; D006632:Histamine; D002217:Carbachol