title: Phenylephrine enhances glutamate release in the medial prefrontal cortex through interaction with N-type Ca2+ channels and release machinery.
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 Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Luo
authors.forename: Si-Hai
authors.initials: SH
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
authors.forename: Wei-Ke
authors.initials: WK
authors.lastname: Deng
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D020864:Calcium Channels, N-Type; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D010656:Phenylephrine; D018698:Glutamic Acid; C023427:guanosine 5'-O-(2-thiodiphosphate); D011493:Protein Kinase C
keywords: glutamate; medial prefrontal cortex; phenylephrine; rat