CANNABINOID RECEPTORS AND MODULATION OF CYCLIC-AMP ACCUMULATION IN THE RAT-BRAIN

被引：180

作者：

BIDAUTRUSSELL, M ^{[1
]}

DEVANE, WA ^{[1
]}

HOWLETT, AC ^{[1
]}

机构：

[1] ST LOUIS UNIV,SCH MED,DEPT PHARMACOL,1402 S GRAND BLVD,ST LOUIS,MO 63104

来源：

JOURNAL OF NEUROCHEMISTRY | 1990年 / 55卷 / 01期

关键词：

Cannabinoid receptor; Cerebellum; Cortex; Cyclic AMP; Hippocampus; Levonantradol; Δ [!sup]9[!/sup]‐Tetrahydrocannabinol;

D O I：

10.1111/j.1471-4159.1990.tb08815.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Abstract: The mechanism by which cannabinoid compounds produce their effects in the rat brain was evaluated in this investigation. Cannabinoid receptors, quantitated by [3H]CP‐55,940 binding, were found in greatest abundance in the rat cortex, cerebellum, hippocampus, and striatum, with smaller but significant binding also found in the hypothalamus, brainstem, and spinal cord. Using rat brain slice preparations, we evaluated the effect of desacetyllevonantradol on basal and forskolin‐stimulated cyclic AMP accumulation in the regions exhibiting the greatest cannabinoid receptor density. Desacetyllevonantradol (10 μM) reduced cyclic AMP levels in the hippocampus, frontal cortex, and striatum. In the cerebellum, however, the response to desacetyllevonantradol was biphasic with cyclic AMP accumulation being decreased at lower and increased at higher concentrations. Desacetyllevonantradol reduced cyclic AMP accumulation in isoproterenol‐stimulated slices in the cortex and cerebellum, but not in the hippocampus. Cells that responded to vasoactive intestinal peptide with an increase in cyclic AMP accumulation in the hippocampus and cortex also responded to desacetyllevonantradol. The modulation of cyclic AMP accumulation by desacetyllevonantradol could be attenuated following stereotaxic implantation of pertussis toxin, supporting the involvement of a G protein in the cannabinoid response in the brain. However, other actions of cannabinoid compounds may also affect the cyclic AMP levels in brain slice preparations. Copyright © 1990, Wiley Blackwell. All rights reserved

引用

页码：21 / 26

页数：6

共 36 条

[21]

HOWLETT AC, 1986, MOL PHARMACOL, V29, P307

[22] CANNABINOID INHIBITION OF ADENYLATE-CYCLASE - RELATIVE ACTIVITY OF CONSTITUENTS AND METABOLITES OF MARIJUANA [J].

HOWLETT, AC .

NEUROPHARMACOLOGY, 1987, 26 (05) :507-512

[23]

JOHNSON MR, 1986, CANNABINOIDS THERAPE, P121

[24]

LEVITT M, 1986, CANNABINOIDS THERAPE, P71

[25]

LITTLE PJ, 1988, J PHARMACOL EXP THER, V247, P1046

[26] NORADRENALINECONTAINING AND VASOACTIVE INTESTINAL PEPTIDE-CONTAINING NEURONAL SYSTEMS IN NEOCORTEX - FUNCTIONAL CONVERGENCE WITH CONTRASTING MORPHOLOGY [J].

MAGISTRETTI, PJ ;

MORRISON, JH .

NEUROSCIENCE, 1988, 24 (02) :367-378

[27]

MARTIN BR, 1986, PHARMACOL REV, V38, P45

[28] BEHAVIORAL-COMPARISONS OF THE STEREOISOMERS OF TETRAHYDROCANNABINOLS [J].

MARTIN, BR ;

BALSTER, RL ;

RAZDAN, RK ;

HARRIS, LS ;

DEWEY, WL .

LIFE SCIENCES, 1981, 29 (06) :565-574

[29]

Mechoulam R, 1986, CANNABINOIDS THERAPE, P1

[30]

MERRITT JC, 1985, MARIHUANA 84, P681

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