The metabotropic glutamate receptor 1 is not involved in the facilitation of glutamate release in cerebrocortical nerve terminals

In this study Lye have addressed the identification of the metabotropic glu tamate receptor (mGluR) involved in the facilitation of glutamate release i n nerve terminals from the cerebral cortex;. mGluR1 and 5 are coupled to ph osphoinositide hydrolysis and the activation of these receptors with the sp ecific agonist 3,5-dihydroxyphenylglycine (DHPG) enhances the release of gl utamate. We have examined whether mGluR1 is responsible for this modulatory effect by preparing nerve terminals from mGluR1 deficient mice. The Ca2+-d ependent glutamate release evoked by a submaximal depolarization is enhance d by the agonist DHPG in nerve terminals from both wild and mutant mice. Th is result is consistent with the finding that the mGluR agonist also induce s a similar increase in the levels of diacylglycerol (DAG) in the nerve ter minals fi om wild and mutant mice. Moreover, the activity-dependent switch from facilitation to inhibition of release. observed when a second stimulat ion of the receptor is applied shortly after (5 min) the first pulse, was a lso observed in the mutant mice. These results indicate therefore, that the facilitation of glutamate release is unlikely to be due to the activation of mGluR1 but related to another phosphoinositide coupled mGluR. (C) 1998 E lsevier Science Ltd. All rights reserved.