Abstract：
:The endogenous cannabinoid anandamide has been reported to produce well-defined behavioral tolerance, but studies on the possible mechanisms underlying this process are few and often contradictory. The present study was designed to survey the cellular events involved in anandamide tolerance, in terms of the effects on receptor number, coupling with G proteins, and activation of the cyclic AMP (cAMP) cascade. Chronic treatment of rats with anandamide (20 mg/kg i.p. for 15 days) resulted in behavioral tolerance without any change in cannabinoid receptor binding in the brain regions studied (striatum, cortex, hippocampus, and cerebellum), suggesting that receptor down-regulation was not involved in the development of anandamide behavioral tolerance. In contrast, prolonged exposure to anandamide significantly reduced agonist-stimulated guanosine 5'-O:-(3-[(35)S]thiotriphosphate) binding in the same areas, with losses of >50%, suggesting that receptor desensitization may be part of the molecular mechanism underlying this tolerance. Finally, concerning the cAMP cascade-the most well-known intracellular signaling pathways activated by CB(1) receptors-in the brain regions from rats tolerant to anandamide, we found no alteration in cAMP levels or in protein kinase A activity. We propose that anandamide, unlike Delta(9)-tetrahydrocannabinol and other cannabinoids, does not alter the receptor system at multiple levels but that desensitization of the CB(1) receptor might account for behavioral tolerance to the drug.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Rubino T,Viganò D,Costa B,Colleoni M,Parolaro Ddoi
10.1046/j.1471-4159.2000.0752478.xkeywords:
subject
Has Abstractpub_date
2000-12-01 00:00:00pages
2478-84issue
6eissn
0022-3042issn
1471-4159journal_volume
75pub_type
杂志文章abstract：:Capillaries in vertebrate brain have unique permeability properties that make up the blood-brain barrier (BBB). Although it is known that capillaries are innervated by nerve endings of intracerebral origin and that brain capillary function is likely acutely regulated by neuronal inputs, the possible mechanisms of neur...
journal_title：Journal of neurochemistry
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abstract：:msec7-1, a mammalian homologue of yeast sec7p, is known as a GDP/GTP exchange factor (GEF) for the ADP ribosylation factor (ARF) family of small GTPases. Here, we report that msec7-1 overexpression in cultured Aplysia neurons leads to an extensive neuritogenesis in a GEF activity-dependent manner through the modulatio...
journal_title：Journal of neurochemistry
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journal_title：Journal of neurochemistry
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journal_title：Journal of neurochemistry
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journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
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journal_title：Journal of neurochemistry
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abstract：:Rat glioma X mouse neuroblastoma hybrid neurotumor cells (NG108-15), synchronized by amino acid deprivation, showed a cell-cycle-dependent peak of activity of a ganglioside N-acetylgalactosaminyl transferase 14-24 h following release from the cell cycle block (S/G2 phase). Maximal expression of two typical lysosomal h...
journal_title：Journal of neurochemistry
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更新日期：1984-04-01 00:00:00
abstract：:The aim of the present study was to gain a deeper insight into the cell signaling pathways involved in the neuroprotection/neurorescue activity of the major green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG). EGCG (1 micro m) caused an immediate (30 min) down-regulation (approximately 40%) of Bad protein level...
journal_title：Journal of neurochemistry
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更新日期：2007-02-01 00:00:00
