Effects of paraventricular nucleus injection of CCK-8 on plasma CCK-8 levels in rats

The aim of the study was to determine whether paraventricular nucleus (PVN) injection of an anorexic 500-pmol dose of cholecystokinin (CCK)-8 could increase plasma CCK-8 levels sufficiently to suppress feeding by a peripheral mechanism. Rats received PVN injections of CCK-8 either alone or with 3H-labelled propionylated CCK-8 (3H-pCCK-8) and plasma samples were taken at various times from 3 to 120 min post-injection. Plasma CCK-8 levels were estimated from measurements of both total plasma CCK-like immunoreactivity (CCK-LI) and 3H-pCCK-8 activity. PVN injections of CCK-8 and 3H-pCCK-8 produced estimated peak increases in plasma CCK-8 of 15+/-11 and 22+/-3 pM, respectively. The i.v. infusion of CCK-8 doses (0.2 and 1 nmol/kg h) that bracketed the threshold dose for suppression of feeding, increased plasma CCK-LI from a basal level of 6+/-1 to 49+/-10 and 166+/-36 pM, respectively. The i.v. injections of 600 and 4800 pmol of CCK-8 did not suppress feeding. These results suggest that PVN injection of an anorexic 500-pmol dose of CCK-8 does not increase plasma CCK-8 levels sufficiently to suppress feeding by a peripheral mechanism.

[1]  V. Go,et al.  Brain Regions Where Cholecystokinin Exerts Its Effect on Satiety a , 1994, Annals of the New York Academy of Sciences.

[2]  W. Creutzfeldt,et al.  Role of cholecystokinin in the negative feedback control of pancreatic enzyme secretion in conscious rats. , 1987, Gastroenterology.

[3]  B. Glenn Stanley,et al.  Brain regions where cholecystokinin suppresses feeding in rats , 2000, Brain Research.

[4]  C. Baile,et al.  Cholecystokinin octapeptide: continuous picomole injections into the cerebral ventricles of sheep suppress feeding. , 1979, Science.

[5]  W. Brugge,et al.  Immunoreactive cholecystokinin in human and rat plasma: correlation of pancreatic secretion in response to CCK , 1984, Regulatory Peptides.

[6]  R. Reidelberger.  Cholecystokinin and control of food intake. , 1994, The Journal of nutrition.

[7]  T. Yaksh,et al.  Intracerebroventricular injections of cholecystokinin octapeptide suppress feeding in rats — pharmacological characterization of this action , 1986, Regulatory Peptides.

[8]  M. Kasuga,et al.  Cholecystokinin octapeptide analogues suppress food intake via central CCK-A receptors in mice. , 1993, The American journal of physiology.

[9]  H. Tsukamoto,et al.  Long-term cannulation model for blood sampling and intragastric infusion in the rat. , 1984, The American journal of physiology.

[10]  R. Reidelberger,et al.  Role of cholecystokinin in the anorexia produced by duodenal delivery of peptone in rats. , 1995, American journal of physiology. Regulatory, integrative and comparative physiology.

[11]  G. Woodruff,et al.  Differentiation of central cholecystokinin receptor binding sites using the non-peptide antagonists MK-329 and L-365,260 , 1990, Brain Research.

[12]  S. Woods,et al.  IVT CCK-8 is more effective than IV CCK-8 at decreasing meal size in the baboon , 1989, Brain Research Bulletin.

[13]  J. Battey,et al.  Differential Gene Expression of CCKA and CCKB Receptors in the Rat Brain , 1993, Molecular and Cellular Neuroscience.

[14]  J. Crawley,et al.  Centrally administered cholecystokinin suppresses feeding through a peripheral-type receptor mechanism. , 1991, The Journal of pharmacology and experimental therapeutics.

[15]  G. Willis,et al.  Ventricular, paraventricular and circumventricular structures involved in peptide-induced satiety , 1984, Regulatory Peptides.

[16]  T. Yaksh,et al.  Sites in the brain at which cholecystokinin octapeptide (CCK-8) acts to suppress feeding in rats: A mapping study , 1990, Neuropharmacology.

[17]  R. Reidelberger,et al.  Comparative effects of CCK-8 on feeding, sham feeding, and exocrine pancreatic secretion in rats. , 1986, The American journal of physiology.

[18]  R. Hill,et al.  Reduction of food intake by central administration of cholecystokinin octapeptide in the rat is dependent upon inhibition of brain peptidases , 1989, British journal of pharmacology.

[19]  S. Leibowitz,et al.  Multiple brain sites sensitive to feeding stimulation by opioid agonists: A cannula-mapping study , 1988, Pharmacology Biochemistry and Behavior.

[20]  C. Baile,et al.  Cholecystokinin antibody injected in cerebral ventricles stimulates feeding in sheep. , 1981, Science.