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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.
A Inui, and
M Okita, and
T Inoue, and
N Sakatani, and
M Oya, and
H Morioka, and
M Oimomi, and
S Baba
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H Morioka, and
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December 1990,
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January 1987,
Peptides,
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August 1991,
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January 1984,
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A Inui, and
M Okita, and
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H Morioka, and
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January 1982,
Peptides,
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May 1993,
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A Inui, and
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H Morioka, and
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April 1989,
Physiology & behavior,
A Inui, and
M Okita, and
T Inoue, and
N Sakatani, and
M Oya, and
H Morioka, and
M Oimomi, and
S Baba
February 1981,
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