Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Lisboa, Portugal.
Eur J Pharmacol. 2009 Nov 25;623(1-3):41-6. doi: 10.1016/j.ejphar.2009.09.020. Epub 2009 Sep 24.
Adenosine A(1) and cannabinoid CB(1) receptors are affected by drugs widely consumed by humans, as it is the case for caffeine, an adenosine receptor antagonist, and tetrahydrocannabinol, a cannabinoid receptor agonist. These receptors are present in the hippocampus and inhibit neurotransmitter release by operating similar transduction mechanisms. We, therefore, evaluated if they cross-talk to modulate synaptic transmission in the hippocampus. To do so, field excitatory postsynaptic potentials (fEPSPs) were recorded from the CA1 area of rat hippocampal slices and the consequences of activation or blockade of cannabinoid CB(1) or adenosine A(1) receptors upon neuromodulation exerted by the other receptor were assessed. The cannabinoid CB(1) receptor agonist, WIN55212-2 (300nM), slowly decreased ( congruent with40%) the fEPSP slope, while the adenosine A(1) receptor agonist, cyclopenthyladenosine (CPA, 15nM) rapidly decreased ( congruent with50%) it. Blockade of cannabinoid CB(1) receptors with AM251 (1microM) did not influence the adenosine A(1) receptor-mediated inhibition of synaptic transmission. Blockade of adenosine A(1) receptors with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 50nM) did not affect the inhibition perpetrated by cannabinoid CB(1) receptor activation. When both receptors were simultaneously activated (5nM CPA plus 300nM WIN55212-2) the net inhibition of synaptic transmission was about the sum of the effect of each drug applied independently. These results indicate independent synaptic transmission modulation by adenosine A(1) and cannabinoid CB(1) receptors at the hippocampus, suggesting that availability of G-proteins coupled to each receptor and availability of other signalling molecules involved in their transducing pathways, are not limiting factors for their modulatory role.
腺苷 A(1) 和大麻素 CB(1) 受体受人类广泛使用的药物影响，如咖啡因，一种腺苷受体拮抗剂，和四氢大麻酚，一种大麻素受体激动剂。这些受体存在于海马体中，并通过操作相似的转导机制抑制神经递质的释放。因此，我们评估了它们是否通过交叉对话来调节海马体中的突触传递。为此，从大鼠海马切片的 CA1 区记录场兴奋性突触后电位 (fEPSP)，并评估大麻素 CB(1) 或腺苷 A(1) 受体的激活或阻断对另一种受体施加的神经调节的后果。大麻素 CB(1) 受体激动剂 WIN55212-2(300nM) 缓慢降低(fEPSP 斜率降低 40%)，而腺苷 A(1) 受体激动剂环戊丙基腺苷 (CPA，15nM) 迅速降低(fEPSP 斜率降低 50%)。用 AM251(1μM) 阻断大麻素 CB(1) 受体不影响腺苷 A(1) 受体介导的突触传递抑制。用 1,3-二丙基-8-环戊基黄嘌呤 (DPCPX，50nM) 阻断腺苷 A(1) 受体不影响大麻素 CB(1) 受体激活引起的抑制作用。当两个受体同时被激活(5nM CPA 加 300nM WIN55212-2)时，突触传递的净抑制作用约为每种药物单独应用的效果之和。这些结果表明，在海马体中，腺苷 A(1) 和大麻素 CB(1) 受体对突触传递具有独立的调节作用，这表明与每个受体偶联的 G 蛋白的可用性和参与其转导途径的其他信号分子的可用性不是其调节作用的限制因素。
