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Journal of Neuroscience, Vol 10, 1070-1081, Copyright © 1990 by Society for Neuroscience
Autoradiographical detection of cholecystokinin-A receptors in primate brain using 125I-Bolton Hunter CCK-8 and 3H-MK-329
DR Hill, TM Shaw, W Graham and GN Woodruff
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, United Kingdom.
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.
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