Colocalization of A2a but not A1 adenosine receptors with GABA-ergic neurons in cardiopulmonary chemoreflex network in the caudal nucleus of the solitary tract.

Zeljka Minic,Donal S O'Leary,Tadeusz J Scislo,Harry G Goshgarian

doi:10.14814/phy2.13913

Abstract

Adenosine operating in the nucleus of the solitary tract (NTS) may inhibit or facilitate neurotransmitter release from nerve terminals and directly inhibit or facilitate central neurons via A1 and A2a pre‐ and postsynaptic receptors, respectively. However, adenosine A2a receptors, may also activate GABA‐ergic neurons/terminals which in turn inhibit glutamatergic transmission in the NTS network. Our previous studies showed that adenosine operating via both A1 (inhibitor) and A2a (activator) receptors powerfully inhibits the cardiopulmonary chemoreflex (CCR) at the level of the caudal NTS. A1 receptors most likely inhibit glutamate release in the CCR network, whereas A2a receptors facilitate NTS GABA‐ergic mechanisms which in turn inhibit CCR glutamatergic transmission. Therefore, we hypothesized that A2a receptors are located on NTS GABA‐ergic neurons/terminals whereas A1 receptors may be located on NTS glutamatergic neurons/terminals. We investigated this hypothesis using double immunofluorescent staining for A2a or A1 adenosine receptors and GABA synthesizing enzyme, GAD67, in 30 μm thick, floating, medullary rat sections. We found that A2a adenosine receptors are localized within the GABA‐ergic cells in the caudal NTS, whereas A1 adenosine receptors are absent from these neurons. Instead, A1 receptors were located on non‐GABA‐ergic (likely glutamatergic) neurons/terminals in the caudal NTS. These data support our functional findings and the hypothesis that adenosine A2a, but not A1 receptors are located on GABA‐ergic neurons.

Highlights

Adenosine is a powerful modulator of cardiovascular reflexes including the arterial baroreflex and cardiopulmonary chemoreflex (CCR) which are primarily integrated in the nucleus of the solitary tract (NTS) (Mosqueda-Garcia et al 1989; Abdel-Rahman and Tao 1996; Spyer and Thomas 2000; Scislo et al 2001, 2008; Scislo and O’Leary 2005; Ichinose et al 2009, 2012; Minic et al 2014b)
The present study demonstrates distinct localization of adenosine A2a and A1 receptor subtypes within the caudal NTS, where the CCR is integrated
A2a adenosine receptors were expressed within GABA-ergic neurons/terminals (Fig. 1), whereas A1 adenosine receptors were localized on non-GABA-ergic neurons some of which may receive GABA-ergic input (Fig. 2)

Summary

Introduction

Adenosine is a powerful modulator of cardiovascular reflexes including the arterial baroreflex and cardiopulmonary chemoreflex (CCR) which are primarily integrated in the nucleus of the solitary tract (NTS) (Mosqueda-Garcia et al 1989; Abdel-Rahman and Tao 1996; Spyer and Thomas 2000; Scislo et al 2001, 2008; Scislo and O’Leary 2005; Ichinose et al 2009, 2012; Minic et al 2014b). Adenosine is released into the NTS during life-threatening situations such as ischemia, hypoxia, and severe hemorrhage (Winn et al 1979; Van Wylen et al.1986; Phillis et al 1987; Yan et al 1995; Scislo and O’Leary 2006; Minic et al 2014a). The accumulated adenosine is released into the extracellular space and envelopes all neurons in the area Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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