Muscarinic Receptors in the Regulation of Cyclic AMP Formation and CREB Phosphorylation in Mouse Prefrontal Cortex
نویسندگان
چکیده
In the prefrontal cortex, dopamine D 1 -like and M 1 muscarinic receptors are both involved in the regulation of attentional, cognitive and emotional processes but so far no information has been provided on their functional interaction. In the present study we show that in mouse medial prefrontal cortex, concomitant activation of M 1 muscarinic receptors potentiated D 1 -like receptor-induced cyclic AMP formation through a mechanism involving activation of G q/11 and the release of G protein subunits. Immunohistochemical studies indicated that the adenylyl cyclase isoforms AC2 and AC4 are expressed in mouse prefrontal cortex and that they colocalize with D 1 -like receptors with a greater association for AC4. In primary cultures of frontal cortex neurons, D 1 -like receptor-induced Ser133 phosphorylation of the transcription factor cyclic AMP-responsive element binding protein (CREB) was potentiated by concurrent stimulation of M 1 receptors. Suppression of AC4 expression with small interfering RNA transfection reduced D 1 stimulation of cyclic AMP formation and CREB phosphorylation and abolished the M 1 potentiation, whereas knockdown of AC2 had no significant Received: July 14, 2011 Accepted after revision: November 9, 2011 Published online: March 28, 2012 Prof. Pierluigi Onali Section of Biochemical Pharmacology, Department of Neuroscience University of Cagliari, Cittadella Universitaria di Monserrato IT–09042 Monserrato (Italy) Tel. +39 070 675 4321, E-Mail onali @ unica.it © 2012 S. Karger AG, Basel 1424–862X/13/0212–0061$38.00/0 www.karger.com/nsg Th is is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercialNoDerivs 3.0 License (www.karger.com/OA-license), applicable to the online version of the article only. Distribution for non-commercial purposes only. D ow nl oa de d by : 54 .7 0. 40 .1 1 11 /7 /2 01 7 2: 10 :4 8 A M
منابع مشابه
Coincidence signaling of dopamine D1-like and M1 muscarinic receptors in the regulation of cyclic AMP formation and CREB phosphorylation in mouse prefrontal cortex.
In the prefrontal cortex, dopamine D1-like and M1 muscarinic receptors are both involved in the regulation of attentional, cognitive and emotional processes but so far no information has been provided on their functional interaction. In the present study we show that in mouse medial prefrontal cortex, concomitant activation of M1 muscarinic receptors potentiated D1-like receptor-induced cyclic ...
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