Abstract
Preliminary studies on CCK receptors in the central nervous system were carried out on guinea pig cerebral cortical synaptoneurosome preparations. In binding assays, the range of affinity of CCK-8, Boc-[Nle28,Nle31]CCK-7, a potent CCK analog, Boc-[Leu31]CCK-4 and of the two benzodiazepine CCK receptor antagonists L-365,260 and MK-329, is in agreement with the presence of CCKB receptors on this model. The effects of Boc-[Nle28,Nle31]CCK-7 on inositol phosphates, cAMP accumulation and 45Ca2+ efflux were investigated. Neither inositol phosphate nor cAMP accumulations could be observed. On the other hand, evidence of Boc-[Nle28,Nle31]CCK-7-, CCK-8- and Boc-[Leu31]CCK-4-induced 45Ca2+ efflux was found in a dose-dependent manner. The CCKB-selective receptor antagonist L-365,260 and, with a weaker efficiency, the CCKA-selective receptor antagonist MK-329, are able to block a maximal effect of Boc-[Nle28,Nle31]CCK-7-induced 45Ca2+ efflux, suggesting that CCKB receptors may regulate calcium ion mobilization.
MeSH terms
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Animals
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Benzodiazepinones / metabolism
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Benzodiazepinones / pharmacology
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Binding Sites
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Calcium / metabolism*
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Cerebral Cortex / drug effects*
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Cerebral Cortex / metabolism
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Cholecystokinin / analogs & derivatives
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Cholecystokinin / metabolism
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Cholecystokinin / pharmacology
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Cyclic AMP / metabolism
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Devazepide
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Guinea Pigs
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Inositol Phosphates / metabolism
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Male
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology
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Phenylurea Compounds*
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Receptors, Cholecystokinin / metabolism*
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Sincalide / analogs & derivatives
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Sincalide / metabolism
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Sincalide / pharmacology
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Synaptosomes / drug effects*
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Synaptosomes / metabolism
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Tetragastrin / analogs & derivatives
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Tetragastrin / metabolism
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Tetragastrin / pharmacology
Substances
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Benzodiazepinones
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Inositol Phosphates
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Peptide Fragments
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Phenylurea Compounds
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Receptors, Cholecystokinin
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Tetragastrin
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butyloxycarbonyl-tryptophyl-leucyl-aspartyl-phenylalaninamide
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L 365260
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Cholecystokinin
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cholecystokinin (27-33), tert-butyloxycarbonyl-Nle(28,31)-
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Cyclic AMP
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Devazepide
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Sincalide
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Calcium