Localization of peripheral cholecystokinin receptors in vivo using the cholecystokinin antagonist [3H](+/-)-MK-329.
Cholecystokinin (CCK) regulates various gastrointestinal functions through specific receptors. The mechanisms responsible for disorders of these functions could be elucidated by non-invasively localizing CCK receptors and quantifying their number in vivo. MK-329 is a highly selective and very high affinity antagonist at the peripheral CCK receptor. We investigated the in vivo binding of [3H](+/-)-MK-329 in mice to determine if binding to CCK receptors could be detected after systemic administration of the tracer. The uptake of [3H](+/-)-MK-329 increased in the pancreas from 5 min to 4 h after administration. The binding was saturable, stereospecific, and more than 80% specific. A total/non-specific binding ratio of 43 was reached at 8 h post-injection. The pancreas was the only organ where specific binding could be detected. Our results suggest that MK-329 labeled with a positron emitter such as C-11 could be used with positron emission tomography to image and quantify peripheral CCK receptors in man.
Sadzot
B
B
Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21205.
Sheldon
J
J
Dannals
R F
RF
Ravert
H T
HT
Wagner
H N
HN
Frost
J J
JJ
D000818:Animals; D001570:Benzodiazepinones / Q000493:pharmacokinetics; D001923:Brain Chemistry / Q000187:drug effects; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010179:Pancreas / Q000378:metabolism; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D014018:Tissue Distribution
D001570:Benzodiazepinones; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D020109:Devazepide