AJP - Regulatory, Integrative and Comparative Physiology, Vol 257, Issue 4 946-R951, Copyright © 1989 by American Physiological Society
Effect of cholecystokinin octapeptide analogues on food intake in the dog
A. Inui, M. Okita, T. Inoue, N. Sakatani, M. Oya, H. Morioka, M. Oimomi and S. Baba
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Cholecystokinin octapeptide, administered into the third cerebral ventricle
(icv), suppresses feeding in sheep, pigs, chicken, rats, and dogs. Because
of the species differences in the feeding response to cholecystokinin
(CCK), we studied the pharmacological characterization of this peptide on
feeding in 16-h-fasted dogs. We examined the effects of CCK-(26-33)-NH2
(CCK-8) and a variety of its analogues, nonsulfated CCK-(26-33)-NH2
(desulfated CCK-8), CCK-(26-33)-OH (deamidated CCK-8),
(Nle28,31)-CCK-(26-33)-NH2 [(Nle28,31)-CCK-8], succinyl-CCK-(27-33)-NH2
(Suc-CCK-7) succinyl-Thr28, Leu29, MePhe33-CCK-(27-33)-NH2 [Suc-Thr28,
Leu29, MePhe33)-CCK-7], CCK-(29-33)-NH2 (CCK-5), and CCK-(30-33)-NH2
(CCK-4) on food intake after iv injection. Systemic dose-response studies
appeared to reveal the following rank order of potencies: Suc-CCK-7 =
Suc-(Thr28, Leu29, MePhe33)-CCK-7 greater than CCK-8 = (Nle28,31)-CCK-8
greater than desulfated CCK-8 greater than deaminated CCK-8 greater than
CCK-5 = CCK-4 = 0. Smaller COOH-terminal fragments acted as antagonists to
the satiety effects of CCK-8. These data demonstrate in the dog that the
structural requirements for the behavioral activity of CCK-8 are the
COOH-terminal amide group, the sulfate ester of the tyrosine moiety, and
the conformational constraints observed in CCK-7.
