Delgado Alejandra, Jaffé Erica H
Laboratorio Neuroquimica, Apartado 20632, CBB, IVIC, Caracas 1020 A, Venezuela.
Int J Cell Biol. 2011;2011:529851. doi: 10.1155/2011/529851. Epub 2011 Jul 12.
We studied the effects of cannabinoids and acute immobilization stress on the regulation of GABA release in the olfactory bulb. Glutamate-stimulated 3H-GABA release was measured in superfused slices. We report that cannabinoids as WIN55, 212-2, methanandamide, and 2-arachidonoylglycerol were able to inhibit glutamate- and KCl-stimulated 3H-GABA release. This effect was blocked by the CB1 antagonist AM281. On the other hand, acute stress was able per se to increase endocannabinoid activity. This effect was evident since the inhibition of stimulated GABA release by acute stress was reversed with AM281 and tetrahydrolipstatin. Inhibition of the endocannabinoid transport or its catabolism showed reduction of GABA release, antagonized by AM281 in control and stressed animals. These results point to endocannabinoids as inhibitory modulators of GABA release in the olfactory bulb acting through an autocrine mechanism. Apparently, stress increases the endocannabinoid system, modulating GABAergic synaptic function in a primary sensory organ.
我们研究了大麻素和急性固定应激对嗅球中γ-氨基丁酸(GABA)释放调节的影响。在灌流切片中测量谷氨酸刺激的3H-GABA释放。我们报告称,大麻素如WIN55,212-2、甲烷酰胺和2-花生四烯酸甘油酯能够抑制谷氨酸和氯化钾刺激的3H-GABA释放。这种作用被CB1拮抗剂AM281阻断。另一方面,急性应激本身能够增加内源性大麻素活性。由于AM281和四氢脂抑素可逆转急性应激对刺激的GABA释放的抑制作用,因此这种作用很明显。抑制内源性大麻素转运或其分解代谢会导致GABA释放减少,在对照动物和应激动物中,AM281可拮抗这种减少。这些结果表明,内源性大麻素是嗅球中GABA释放的抑制性调节剂,通过自分泌机制发挥作用。显然,应激会增加内源性大麻素系统,调节初级感觉器官中的GABA能突触功能。