EVIDENCE THAT CHOLECYSTOKININ INDUCES IMMEDIATE-EARLY GENE-EXPRESSION IN THE BRAIN-STEM, HYPOTHALAMUS AND AMYGDALA OF THE RAT BY A CCKA RECEPTOR MECHANISM

被引:106
作者
DAY, HEW [1 ]
MCKNIGHT, AT [1 ]
POAT, JA [1 ]
HUGHES, J [1 ]
机构
[1] ADDENBROOKES HOSP,PARKE DAVIS NEUROSCI RES CTR,CAMBRIDGE CB2 2QB,ENGLAND
关键词
CHOLECYSTOKININ; CCKA RECEPTOR; CCKB RECEPTOR; DEVAZEPIDE; CI-988; VAGUS; NTS; HYPOTHALAMUS; IMMEDIATE EARLY GENE; C-FOS;
D O I
10.1016/0028-3908(94)90111-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The effect of sulphated cholecystokinin octapeptide (CCK-8S) on immediate early gene expression in the rat CNS was investigated using the technique of in situ hybridization. A rapid and transient induction of c-fos, NGFI-A and NGFI-B (nerve growth factor-induced genes A and B) mRNA was demonstrated in the nucleus tractus solitarius (NTS), area postrema (AP), hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, and central nucleus of the amygdala, following peripheral administration of CCK-8S (1-100 mu g/kg i.p.). In contrast, levels of c-jun, jun B and jun D mRNA were unaffected by the peptide. The closely related decapeptide, caerulein (50 mu g/kg i.p.), induced the same pattern of IEG expression as CCK-8S, whereas the desulphated octapeptide, CCK-8DS (50 mu g/kg i.p.), had no effect on levels of mRNA for any IEG studied. Expression of IEG mRNA in these areas was suppressed by bilateral subdiaphragmatic vagotomy, and by pretreatment with the selective CCKA receptor antagonist, devazepide (0.1 and 1 mg/kg i.p.). In contrast, CCK-8S induction of IEG mRNA was not blocked by pretreatment with the selective CCKB receptor antagonist, CI-988 (1 or 10 mg/kg i.p.). In addition, the selective CCKB receptor agonists, CCK-4 (50 mu g/kg i.p.) or pentagastrin (2 mg/kg i.p.), failed to induce IEG expression in any of the areas studied. These results suggest that systemic CCK-8S primarily acts via CCKA receptors on vagal afferents to stimulate IEG mRNA expression in the rat CNS.
引用
收藏
页码:719 / 727
页数:9
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