Colocalization of A 2a but not A 1 adenosine receptors with GABA-ergic neurons in cardiopulmonary chemoreflex network in the caudal nucleus of the solitary tract

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 A and A pre- and postsynaptic receptors, respectively. However, adenosine A 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 A (inhibitor) and A (activator) receptors powerfully inhibits the cardiopulmonary chemoreflex (CCR) at the level of the caudal NTS. A receptors most likely inhibit glutamate release in the CCR network, whereas A receptors facilitate NTS GABA-ergic mechanisms which in turn inhibit CCR glutamatergic transmission. Therefore, we hypothesized that A receptors are located on NTS GABA-ergic neurons/terminals whereas A receptors may be located on NTS glutamatergic neurons/terminals. We investigated this hypothesis using double immunofluorescent staining for A or A adenosine receptors and GABA synthesizing enzyme, GAD67, in 30 μm thick, floating, medullary rat sections. We found that A adenosine receptors are localized within the GABA-ergic cells in the caudal NTS, whereas A adenosine receptors are absent from these neurons. Instead, A 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 A but not A receptors are located on GABA-ergic neurons.