Influence of central and peripheral administration of pancreatic polypeptide on gastric mucosa growth.
Previous studies have shown that pancreatic polypeptide (PP) inhibits exocrine pancreatic secretion. The aim of present study was to determine the influence of PP administration on gastric growth and blood flow.


METHODS
Study was performed on regularly fed, fasted or fasted and subsequently refed rats. Rats were treated with saline (intraperitoneally - i.p.), caerulein (0.24 nmol/kg/dose, i.p.), pentagastrin (0.38 micromol/kg/dose, i.p.) or PP (5 nmol/kg/dose, i.p. or 10 pmol/dose intracerebroventricularly - i.c.v.). Saline, caerulein, pentagastrin and PP were administered alone or in combination, 3 times daily during last 48 h of experiment.


RESULTS
Treatment with pentagastrin increased gastric mucosa weight, mucosal DNA synthesis and gastric blood flow in all group tested. Intraperitoneal and i.c.v administration of PP alone reduced mucosal DNA synthesis in regularly fed and refed animals, and decreased gastric blood flow in refed animals. Combination of PP i.p. or i.c.v plus pentagastrin significantly reduced the pentagastrin-evoked increase in gastric mucosa weight, gastric DNA synthesis and gastric blood flow in fasted animals, as well as regularly fed animals. In refed animals, influence of PP administration on the pentagastrin-evoked increase in gastric mucosa weight was weak and statistically insignificant, but still i.p or i.c.v administration of PP significantly reduced gastric blood flow and mucosal DNA synthesis in this group of animals. Administration of caerulein caused weak, but significant increase in gastric DNA synthesis, gastric mucosa weight and gastric blood flow in fasted rats. In regularly fed animals, caerulein significantly increased only gastric DNA synthesis and gastric blood flow. In fasted animals with subsequent refeeding, caerulein was without effect on parameters tested in the stomach. Neither i.p. nor i.c.v administration of PP affected the caerulein-evoked effects in the stomach.


CONCLUSIONS
Peripheral and central administration of PP inhibits food- and pentagastrin-stimulated growth of gastric mucosa. Similar effects of low central doses of PP as the high peripheral doses of PP suggests a crucial role of the central nervous system in the inhibitory effect of PP on gastric mucosa growth.
Dembiński
A
A
Department of Physiology, Jagiellonian University Medical College, Cracow, Poland. mpdembin@cyf-kr.edu.pl
Warzecha
Z
Z
Ceranowicz
P
P
Pawlik
M
M
Dembiński
M
M
Kabat
K
K
Konturek
S J
SJ
Kownacki
P
P
Hładki
W
W
Pawlik
W W
WW
D000818:Animals; D002108:Ceruletide / Q000008:administration & dosage / Q000493:pharmacokinetics; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005508:Food Deprivation / Q000502:physiology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000254:growth & development*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D008722:Methods; D010191:Pancreatic Polypeptide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism; D010418:Pentagastrin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D010191:Pancreatic Polypeptide; D002108:Ceruletide; D004247:DNA; D010418:Pentagastrin