Effect of intestinal inhibitory peptides on vagally induced secretion from isolated perfused porcine pancreas.
Several gastrointestinal peptides inhibit pancreatic secretion in intact animals, but fail to do so in isolated pancreas preparations. Using isolated perfused porcine pancreas with intact innervation, we studied the influence of such peptides (somatostatin, peptide YY, glucagon-like peptide-1, oxyntomodulin, neuropeptide Y, galanin, and calcitonin gene-related peptide) on vagally induced secretion and on release of vasoactive intestinal polypeptide (VIP), a neuropeptide involved in fluid and bicarbonate secretion. In control experiments electrical vagus stimulation increased flow of juice from 0.9 +/- 0.1 to 37.3 +/- 5.6 ml/h and protein output from 43 +/- 5 to 1,244 +/- 336 mg/h (mean +/- SD). With somatostatin-14 at 10(-10) mol/L, the fluid response was reduced to 64 +/- 11% of controls, protein concentration to 78 +/- 3.8%, and protein output to 50 +/- 5% (p < 0.05). At 10(-8) M the response was almost abolished. VIP release, which in control experiments increased from 0.2 +/- 0.05 to 2.1 +/- 0.4 pmol/min, was similarly reduced (p < 0.01). Galanin at 10(-8) M inhibited the fluid response to 54 +/- 7% of controls, protein output to 51.7 +/- 11%, and VIP release to 54 +/- 6% (p < 0.01). None of the other inhibitory peptides affected vagus responses. It is concluded that somatostatin and galanin inhibit pancreatic secretion through interaction with intrapancreatic ganglia. The other peptides act on extrapancreatic, possibly central sites.
Holst
J J
JJ
Department of Medical Physiology C, Panum Institute, Copenhagen, Denmark.
Rasmussen
T N
TN
Harling
H
H
Schmidt
P
P
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004558:Electric Stimulation; D019004:Galanin; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides / Q000494:pharmacology; D066298:In Vitro Techniques; D009478:Neuropeptide Y / Q000494:pharmacology; D053772:Oxyntomodulin; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D019894:Peptide YY; D010455:Peptides / Q000494:pharmacology*; D010477:Perfusion; D011498:Protein Precursors / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology; D013552:Swine; D014630:Vagus Nerve / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D009478:Neuropeptide Y; D053772:Oxyntomodulin; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D019894:Peptide YY; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D004763:Glucagon-Like Peptides; D019004:Galanin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D015740:Calcitonin Gene-Related Peptide