Phenylephrine enhances glutamate release in the medial prefrontal cortex through interaction with N-type Ca2+ channels and release machinery

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Abstract

α1-adrenoceptors (α1-ARs) stimulation has been found to enhance excitatory processes in many brain regions. A recent study in our laboratory showed that α1-ARs stimulation enhances glutamatergic transmission via both pre- and post-synaptic mechanisms in layer V/VI pyramidal cells of the rat medial prefrontal cortex (mPFC). However, a number of pre-synaptic mechanisms may contribute to α1-ARs-induced enhancement of glutamate release. In this study, we blocked the possible post-synaptic action mediated by α1-ARs to investigate how α1-ARs activation regulates pre-synaptic glutamate release in layer V/VI pyramidal neurons of mPFC. We found that the α1-ARs agonist phenylephrine (Phe) induced a significant enhancement of glutamatergic transmission. The Phe-induced potentiation was mediated by enhancing pre-synaptic glutamate release probability and increasing the number of release vesicles via a protein kinase C-dependent pathway. The mechanisms of Phe-induced potentiation included interaction with both glutamate release machinery and N-type Ca2+ channels, probably via a pre-synaptic Gq/phospholipase C/protein kinase C pathway. Our results may provide a cellular and molecular mechanism that helps explain α1-ARs-mediated influence on PFC cognitive functions.

Alpha1-adrenoceptor (α1-ARs) stimulation has been reported to enhance glutamatergic transmission in layer V/VI pyramidal neurons of the rat medial prefrontal cortex (mPFC). We found that α1-ARs agonist phenylephrine (Phe) increases pre-synaptic glutamate release probability and the number of released vesicles via interaction with both glutamate release machinery and N-type Ca2+ channels. Our results may provide a cellular and molecular mechanism that helps explain α1-ARs-mediated influence on PFC cognitive functions. Gq, Gq protein; PLC, phospholipase C; PKC, protein kinase C; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; NMDA, N-methyl-d-aspartate; Glu, glutamate; Phe, phenylephrine.

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