Mechanism of actions of cholecystokinin octapeptide on food intake and insulin and pancreatic polypeptide release in the dog.
We investigated the mechanism by which CCK-8 injected into the third cerebral ventricle (ITV administration) inhibits food intake and stimulates insulin and pancreatic polypeptide (PP) secretion in the dog. ITV administration of CCK-8 (4.08 micrograms/5 min) resulted in a significant elevation of plasma insulin and PP concentrations. This effect was abolished by truncal vagotomy and promptly inhibited by ITV administration of atropine (20 micrograms) and proglumide (10 mg). CCK-8 was less effective in increasing insulin and PP concentrations than in reducing feeding. Thus, 1.36 micrograms of ITV CCK-8 markedly reduced food intake to 14, 15, 29 and 31% of control values at 10, 30, 60 and 120 min, respectively. Atropine and naloxone (50 micrograms) had no blocking effect on CCK-8-induced satiety, whereas proglumide antagonized it. These results indicate that ITV CCK-8 effects the endocrine pancreas and food intake through atropine-sensitive and atropine-insensitive mechanisms, respectively, both of which are likely to be mediated by CNS CCK receptors. Intravenous CCK-8 also stimulated PP and insulin release, through mechanisms that were atropine-sensitive and atropine-insensitive, respectively. However, its mode of action, especially on insulin secretion, was quite different from that of ITV CCK-8. Therefore, exogenous CCK appears to act in the brain and the periphery in concert with and independently from cholinergic systems.
Inui
A
A
Second Department of Internal Medicine, School of Medicine, Kobe University, Japan.
Okita
M
M
Inoue
T
T
Sakatani
N
N
Oya
M
M
Morioka
H
H
Ogawa
T
T
Mizuno
N
N
Baba
S
S
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004435:Eating / Q000187:drug effects*; D007276:Injections, Intraventricular; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D010191:Pancreatic Polypeptide / Q000097:blood / Q000378:metabolism*; D011377:Proglumide / Q000494:pharmacology; D012016:Reference Values; D012844:Sincalide / Q000008:administration & dosage / Q000494:pharmacology*; D014628:Vagotomy
D007328:Insulin; D010191:Pancreatic Polypeptide; D001285:Atropine; D011377:Proglumide; D012844:Sincalide