Autoradiographical detection of cholecystokinin-A receptors in primate brain using 125I-Bolton Hunter CCK-8 and 3H-MK-329.
In vitro autoradiography was performed in order to visualize cholecystokinin-A (CCK-A) receptors in sections of Cynomolgus monkey brain. CCK-A receptors were defined as those which displayed high affinity for the selective non-peptide antagonist MK-329 (L-364,718) and were detected in several regions by selective inhibition of 125I-Bolton Hunter CCK using MK-329 or direct labeling with 3H-MK-329. In the caudal medulla, high densities of CCK-A sites were present in the nucleus tractus solitarius, especially the caudal and medial aspects, and also the dorsal motor nucleus of the vagus. CCK-A sites were localized to a number of hypothalamic nuclei such as the supraoptic and paraventricular nuclei, the dorsomedial and infundibular nuclei as well as the neurohypophysis. The mammillary bodies and supramammillary nuclei also contained CCK-A receptor sites. High concentrations of CCK-A receptors were present in the substantia nigra zona compacta and also the ventral tegmental area and may be associated with dopamine cell bodies. Binding of 3H-MK-329 was also detected in parts of the caudate nucleus and ventral putamen. The detection, by autoradiographical means, of CCK-A receptors throughout the Cynomolgus monkey brain contrasts with similar studies performed using rodents and suggests differences in the density and, perhaps, the importance of CCK-A receptors in the primate as opposed to the rodent. The data suggest the possibility that CCK-A receptors may be involved in a number of important brain functions as diverse as the processing of sensory information from the gut, the regulation of hormone secretion, and the activity of dopamine cell activity.
Hill
D R
DR
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, United Kingdom.
Shaw
T M
TM
Graham
W
W
Woodruff
G N
GN
D000818:Animals; D001345:Autoradiography; D001479:Basal Ganglia / Q000378:metabolism; D001570:Benzodiazepinones; D001921:Brain / Q000378:metabolism*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors; D020109:Devazepide; D007031:Hypothalamus / Q000378:metabolism; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D008252:Macaca fascicularis; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D012844:Sincalide / Q000031:analogs & derivatives*; D013378:Substantia Nigra / Q000378:metabolism; D013388:Succinimides; D014316:Tritium
D001570:Benzodiazepinones; C044758:Bolton Hunter-cholecystokinin octapeptide; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D011949:Receptors, Cholecystokinin; D013388:Succinimides; D014316:Tritium; D002766:Cholecystokinin; D020109:Devazepide; D012844:Sincalide