Serotonin3 receptor antagonists block anorectic responses to amino acid imbalance.
The role of serotonin3 (5-HT3) receptors in the initial food intake depression of rats ingesting amino acid imbalanced or high-protein diets was investigated. The 5-HT antagonists metergoline, pirenpirone, ICS 205-930, and MDL 72222, the dopamine antagonist pimozide, or the alpha-adrenergic antagonist phentolamine were injected 15-45 min before presentation of test diets. Food intake was measured at intervals for 3 days. The 5-HT3 antagonists, ICS 205-930 and MDL 72222, restored feeding of a mild isoleucine (Ile)-imbalanced diet to control levels, although MDL 72222 had a longer time course of action. ICS 205-930 also increased intake of a severe Ile-imbalanced diet and Thr-imbalanced diet but not a high-protein (44% casein) diet. Treatment with metergoline, which blocks 5-HT1, 5-HT2, and dopamine receptor sites but not 5-HT3 sites, increased intake of the basal diet at 3 and 6 h but did not significantly alter intake of the mild Ile-imbalanced diet. Although pimozide tended to increase intake of the mild imbalanced diet, neither dopamine nor alpha-adrenergic receptor antagonism significantly affected imbalanced diet intake. Thus 5-HT3 receptors may mediate the anorexigenic activity of 5-HT associated with feeding an amino acid-imbalanced diet.
Hammer
V A
VA
Department of Physiological Sciences, School of Veterinary Medicine, University of California, Davis 95616.
Gietzen
D W
DW
Beverly
J L
JL
Rogers
Q R
QR
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D000855:Anorexia / Q000378:metabolism*; D004032:Diet; D004044:Dietary Proteins / Q000494:pharmacology; D001068:Feeding and Eating Disorders / Q000378:metabolism*; D007532:Isoleucine / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013912:Threonine / Q000008:administration & dosage / Q000378:metabolism
D000596:Amino Acids; D004044:Dietary Proteins; D012702:Serotonin Antagonists; D007532:Isoleucine; D010868:Pimozide; D013912:Threonine; D010646:Phentolamine