Llansola M, Hermenegildo C, Miñana M D, Felipo V
Instituto de Investigaciones Citologicas de la Fundación Valenciana de Investigaciones Biomédicas, Valencia, Spain.
Neurochem Res. 1998 Jun;23(6):913-8. doi: 10.1023/a:1022423415238.
We observed that AP-3, an antagonist of metabotropic glutamate receptors, reduced carbachol-induced hydrolysis of phospholipids in hippocampal slices. This inhibition could be explained in different ways, e.g.: 1) AP-3 acts also as antagonist of muscarinic receptors mediating the hydrolysis of phospholipids induced by carbachol, 2) Carbachol induces the release of glutamate which, by activating metabotropic glutamate receptors, leads to additional hydrolysis of phospholipids. The aim of this work was to test these possibilities. It is shown that AP-3 reduces carbachol-induced hydrolysis of phospholipids in hippocampal slices but not in cerebellar neurons at 10-14 days of culture, when these cells are not able to induce hydrolysis of phospholipids following activation of metabotropic glutamate receptors. It is also shown that carbachol induces a release of [3H]aspartate in hippocampal slices. The results reported suggest that the hydrolysis of phospholipids induced by carbachol in hippocampal slices would have two components. One part would be due to direct activation by carbachol of muscarinic receptors associated to activation of phospholipase C. This part would not be inhibited by AP-3. The second part would be due to subsequent release of glutamate and activation of metabotropic glutamate receptors. This part would be inhibited by AP-3.
我们观察到，代谢型谷氨酸受体拮抗剂AP - 3可降低海马脑片中卡巴胆碱诱导的磷脂水解。这种抑制作用可以用不同方式来解释，例如：1）AP - 3还作为毒蕈碱受体拮抗剂，介导卡巴胆碱诱导的磷脂水解；2）卡巴胆碱诱导谷氨酸释放，通过激活代谢型谷氨酸受体，导致磷脂进一步水解。本研究的目的是验证这些可能性。结果表明，在培养10 - 14天的海马脑片中，AP - 3可降低卡巴胆碱诱导的磷脂水解，但在小脑神经元中则无此作用，此时这些细胞在代谢型谷氨酸受体激活后无法诱导磷脂水解。研究还表明，卡巴胆碱可诱导海马脑片中[3H]天冬氨酸的释放。报道的结果提示，海马脑片中卡巴胆碱诱导的磷脂水解有两个成分。一部分是由于卡巴胆碱直接激活与磷脂酶C激活相关的毒蕈碱受体。这部分不会被AP - 3抑制。第二部分是由于随后谷氨酸的释放和代谢型谷氨酸受体的激活。这部分会被AP - 3抑制。
