Pharmacokinetics and feeding responses to muramyl dipeptide in rats.
N-acetyl-muramyl-L-alanine-D-isoglutamine or muramyl dipeptide (MDP) is the minimally active subunit of bacterial peptidoglycan. During a systemic infection, the involvement of MDP has been demonstrated in food intake depression by the macrophage hydrolysis of Gram-positive bacteria. Under normal conditions, mammals are constantly exposed to the release of endogenous MDP from degraded gut flora and that of exogenous MDP from the diet. However, MDP digestion and absorption in the gastrointestinal tract are not fully understood, and their physiological significance needs to be clarified. After gavage (1.5 mg/kg), very low levels of MDP were found in the systemic circulation of rats and feeding patterns were not altered. In contrast, after the intraperitoneal injection of a similar dose, a depression in food intake was observed. The rats reduced their meal frequency and constant feeding rate, showing signs of satiety. The behavioral satiety sequence (BSS) was modified by behavioral changes, similar to those which appear during sickness, such as an increase in resting and a reduction in grooming. Our data suggest that the hypophagic effect of MDP may result from satiety and sickness behavior.
Fosset
Sophie
S
Unité INRA/INAPG de Physiologie de la Nutrition et du Comportement Alimentaire, Institut National Agronomique de Paris-Grignon, 16 rue Claude Bernard, F-75231, Paris, France.
Fromentin
Gilles
G
Rampin
Olivier
O
Lang
Vincent
V
Mathieu
Florence
F
Tomé
Daniel
D
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004435:Eating / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007441:Intubation, Gastrointestinal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012146:Rest; D012528:Satiety Response / Q000187:drug effects
D000119:Acetylmuramyl-Alanyl-Isoglutamine