EVALUATION OF CAMP INVOLVEMENT IN CANNABINOID-INDUCED ANTINOCICEPTION

被引:14
作者
COOK, SA [1 ]
WELCH, SP [1 ]
LICHTMAN, AH [1 ]
MARTIN, BR [1 ]
机构
[1] VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, DEPT PHARMACOL & TOXICOL, RICHMOND, VA 23298 USA
关键词
ANTINOCICEPTION; CANNABINOIDS; MPE; CAMP;
D O I
10.1016/0024-3205(95)00188-C
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
It has been proposed that cannabinoids act at a Gi protein-coupled receptor to produce antinociception. One action of Gi-proteins is to decrease intracellular cAMP via inhibition of adenylyl cyclase activity. Although cannabinoid inhibition of forskolin-stimulated adenylyl cyclase is used as a confirmation of functional cannabinoid receptors, it is unknown whether this second messenger system specifically mediates cannabinoid-induced antinociception. This in vivo study was conducted using enantiomeric cAMP analogs, Rp-cAMPS (an antagonist) and Sp-cAMPS (an agonist), and the cAMP agonist Cl-cAMP to test the hypothesis that cannabinoid-induced antinociception is due to decreased adenylyl cyclase activity. None of the cAMP analogs, forskolin, or 1,9-dideoxy-forskolin affected Delta(9)-THC or CP-55,940-induced antinociception produced by intrathecal (i.t.) or intracerebroventricular (i.c.v.) injections in mice. Experiments were also conducted to investigate whether i.c.v. administration of Sp-cAMPS would block i.c.v. cannabinoid-induced antinociception in rats. Sp-cAMPS failed to block CP-55,940-induced antinociception. However, Sp-cAMPS produced hyper-excitability and reactive behavior indicating that it did elicit a pharmacological effect. Although, adenylyl cyclase may mediate other cannabinoid-induced actions, these results do antinociception. Alternatively, other effector systems such as calcium or potassium channels coupled to cannabinoid receptors may mediate cannabinoid-induced antinociception.
引用
收藏
页码:2049 / 2056
页数:8
相关论文
共 28 条
  • [1] HYDROLYSIS OF CYCLIC-NUCLEOTIDES BY A PURIFIED CGMP-STIMULATED PHOSPHODIESTERASE - STRUCTURAL REQUIREMENTS FOR HYDROLYSIS
    BRAUMANN, T
    ERNEUX, C
    PETRIDIS, G
    STOHRER, WD
    JASTORFF, B
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1986, 871 (02) : 199 - 206
  • [2] BROWN MA, 1990, ANNU REV PHYSIOL, P197
  • [3] CANNABINOID RECEPTOR AGONISTS INHIBIT CA CURRENT IN NG108-15 NEUROBLASTOMA-CELLS VIA A PERTUSSIS TOXIN-SENSITIVE MECHANISM
    CAULFIELD, MP
    BROWN, DA
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1992, 106 (02) : 231 - 232
  • [4] COMPTON DR, 1993, J PHARMACOL EXP THER, V265, P218
  • [5] CONNELLY PA, 1987, J BIOL CHEM, V262, P4324
  • [6] 8-(4-CHLOROPHENYL)THIO-CYCLIC AMP IS A POTENT INHIBITOR OF THE CYCLIC GMP-SPECIFIC PHOSPHODIESTERASE (PDE-VA)
    CONNOLLY, BJ
    WILLITS, PB
    WARRINGTON, BH
    MURRAY, KJ
    [J]. BIOCHEMICAL PHARMACOLOGY, 1992, 44 (12) : 2303 - 2306
  • [7] D'amour FE, 1941, J PHARMACOL EXP THER, V72, P74
  • [8] DEWEY WL, 1986, PHARMACOL REV, V38, P151
  • [9] DEWIT RJW, 1984, EUR J BIOCHEM, V142, P255
  • [10] HARRIS LS, 1964, J PHARMACOL EXP THER, V143, P141