Premium
A 2a adenosine receptors modulate cardiopulmonary chemoreflex control of regional sympathetic outputs via activation of GABAergic neurons within the caudal portion of the nucleus of the solitary tract (cNTS): functional and anatomical evidence
Author(s) -
Minic Zeljka,
Llewellyn-Smith Ida J,
OˈLeary Donal S,
Scislo Tadeusz J
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1091.28
Subject(s) - gabaergic , colocalization , receptor , adenosine , neuroscience , stimulation , adenosine a1 receptor , adenosine receptor , chemistry , medicine , biology , endocrinology , agonist
The cardiopulmonary chemoreflex (CCR) may contribute to severe hypotension and sudden cardiac death when markedly activated. Since adenosine is released into the central nervous system during life threatening ischemia, we hypothesized that it may serve as a central negative feedback regulator for this reflex integrated in the cNTS. We have shown that CCR evoked sympathoinhibition was markedly attenuated after stimulation of A 2a adenosine receptors in the cNTS ( FASEB J 24: 624.11, 2010) and this attenuation was virtually abolished by GABAergic blockade ( FASEB J 25: 844.3, 2011). These data imply that GABAergic neurons/terminals within cNTS express A 2a receptors. We investigated this hypothesis using double immunofluorescent staining for A 2a receptors (Cy3, red) and GAD67, the GABA synthetic enzyme (FITC, green). We observed extensive colocalization of A 2a receptors with GABAergic neurons in the cNTS while we observed no such colocalization in more caudal portions of the medulla. These data support our functional findings that A 2a adenosine receptors inhibit CCR responses by facilitating GABA release from nerve terminals in the cNTS. HL‐67814