Intestinal transit of fat depends on accelerating effect of cholecystokinin and slowing effect of an opioid pathway.
Fat has been described to both accelerate and slow intestinal transit. We hypothesized that the fat-induced jejunal brake depends on the combined accelerating effect of CCK and the slowing effect of an opioid pathway. Using a multifistulated model, intestinal transit was measured in four dogs, while 60 mM oleate was delivered into the proximal gut with either 0 or 6 mg naloxone, and 0.1 mg/kg devazepide (a peripheral CCK-A-receptor antagonist) administered intraluminally and intravenously, respectively. In a second study, intestinal transit was measured in seven dogs, while naloxone was delivered intraluminally at 0-, 3-, 6-, or 12-mg doses. Compared to the jejunal brake (marker recovery of 50.1 +/- 2.6%), intestinal transit was slowed by the CCK-A antagonist (36.4 +/- 8.3%; P < 0.05) and accelerated by naloxone (82.0 +/- 6.8%; P < 0.05). The accelerating effect of CCK occurred early in the transit response, while the dose-dependent effect (P < 0.05) of naloxone occurred later. We conclude that fat-induced jejunal brake depends on the early accelerating effect of CCK and the later slowing effect of a naloxone-sensitive opioid pathway.
Lin
Henry C
HC
Department of Medicine, Cedars-Sinai Medical Center, CSMC Burns & Allen Research Institute, Los Angeles, California 90048, USA.
Zaidel
Oren
O
Hum
Susan
S
D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D020109:Devazepide / Q000494:pharmacology; D004041:Dietary Fats / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology*; D007583:Jejunum / Q000187:drug effects / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D019301:Oleic Acid / Q000378:metabolism; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology; D011957:Receptors, Opioid / Q000502:physiology*
D004041:Dietary Fats; D009292:Narcotic Antagonists; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D011957:Receptors, Opioid; D019301:Oleic Acid; D009270:Naloxone; D002766:Cholecystokinin; D020109:Devazepide