Department of Physiology, Dental School, Center for Pharmacological and Botanical Studies, National Council of Scientific and Technical Research, University of Buenos Aires, Buenos Aires, Argentina.
Braz J Med Biol Res. 2009 Jun;42(6):537-44. doi: 10.1590/s0100-879x2009000600010.
Our objective was to determine the effect of arachidonylethanolamide (anandamide, AEA) injected intracerebroventricularly (icv) into the lateral ventricle of the rat brain on submandibular gland (SMG) salivary secretion. Parasympathetic decentralization (PSD) produced by cutting the chorda tympani nerve strongly inhibited methacholine (MC)-induced salivary secretion while sympathetic denervation (SD) produced by removing the superior cervical ganglia reduced it slightly. Also, AEA (50 ng/5 microL, icv) significantly decreased MC-induced salivary secretion in intact rats (MC 1 microg/kg: control (C), 5.3 +/- 0.6 vs AEA, 2.7 +/- 0.6 mg; MC 3 microg/kg: C, 17.6 +/- 1.0 vs AEA, 8.7 +/- 0.9 mg; MC 10 microg/kg: C, 37.4 +/- 1.2 vs AEA, 22.9 +/- 2.6 mg). However, AEA did not alter the significantly reduced salivary secretion in rats with PSD, but decreased the slightly reduced salivary secretion in rats with SD (MC 1 microg/kg: C, 3.8 +/- 0.8 vs AEA, 1.4 +/- 0.6 mg; MC 3 microg/kg: C, 14.7 +/- 2.4 vs AEA, 6.9 +/- 1.2 mg; P < 0.05; MC 10 microg/kg: C, 39.5 +/- 1.0 vs AEA, 22.3 +/- 0.5 mg; P < 0.001). We showed that the inhibitory effect of AEA is mediated by cannabinoid type 1 CB1 receptors and involves GABAergic neurotransmission, since it was blocked by previous injection of the CB1 receptor antagonist AM251 (500 ng/5 microL, icv) or of the GABA A receptor antagonist, bicuculline (25 ng/5 microL, icv). Our results suggest that parasympathetic neurotransmission from the central nervous system to the SMG can be inhibited by endocannabinoid and GABAergic systems.
我们的目的是确定脑室内注射花生四烯酸乙醇酰胺（大麻素，AEA）对大鼠下颌下腺（SMG）唾液分泌的影响。切断鼓索神经产生的副交感神经去神经支配（PSD）强烈抑制了乙酰甲胆碱（MC）诱导的唾液分泌，而去除颈上神经节产生的交感神经去神经支配（SD）则轻微减少了这种分泌。此外，AEA（50ng/5μL，脑室内注射）显著降低了完整大鼠中 MC 诱导的唾液分泌（MC1μg/kg：对照（C），5.3±0.6vsAEA，2.7±0.6mg；MC3μg/kg：C，17.6±1.0vsAEA，8.7±0.9mg；MC10μg/kg：C，37.4±1.2vsAEA，22.9±2.6mg）。然而，AEA 并没有改变 PSD 大鼠中明显减少的唾液分泌，但降低了 SD 大鼠中略减少的唾液分泌（MC1μg/kg：C，3.8±0.8vsAEA，1.4±0.6mg；MC3μg/kg：C，14.7±2.4vsAEA，6.9±1.2mg；P<0.05；MC10μg/kg：C，39.5±1.0vsAEA，22.3±0.5mg；P<0.001）。我们表明，AEA 的抑制作用是通过大麻素 1 型 CB1 受体介导的，并涉及 GABA 能神经传递，因为它被 CB1 受体拮抗剂 AM251（500ng/5μL，脑室内注射）或 GABA A 受体拮抗剂 Bicuculline（25ng/5μL，脑室内注射）的预先注射所阻断。我们的结果表明，来自中枢神经系统的副交感神经传递可以被内源性大麻素和 GABA 能系统抑制。
