NTS adenosine A2a receptors inhibit the cardiopulmonary chemoreflex control of regional sympathetic outputs via a GABAergic mechanism.

Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901228 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1539 (Electronic) Linking ISSN: 03636135 NLM ISO Abbreviation: Am J Physiol Heart Circ Physiol Subsets: MEDLINE

Original Publication: Bethesda, Md. : American Physiological Society,

Biguanides/*pharmacology ; Receptor, Adenosine A2A/*metabolism ; Receptors, GABA-A/*metabolism ; Receptors, GABA-B/*metabolism ; Reflex/*physiology ; Serotonin Receptor Agonists/*pharmacology ; Solitary Nucleus/*metabolism ; Sympathetic Nervous System/*metabolism; Adenosine/analogs & derivatives ; Adenosine/pharmacology ; Adenosine A2 Receptor Agonists/pharmacology ; Animals ; Bicuculline/pharmacology ; GABA Antagonists/pharmacology ; Heart/drug effects ; Microinjections ; Morpholines/pharmacology ; Phenethylamines/pharmacology ; Rats ; Reflex/drug effects ; Sympathetic Nervous System/drug effects

Adenosine is a powerful central neuromodulator acting via opposing A1 (inhibitor) and A2a (activator) receptors. However, in the nucleus of the solitary tract (NTS), both adenosine receptor subtypes attenuate cardiopulmonary chemoreflex (CCR) sympathoinhibition of renal, adrenal, and lumbar sympathetic nerve activity and attenuate reflex decreases in arterial pressure and heart rate. Adenosine A1 receptors inhibit glutamatergic transmission in the CCR pathway, whereas adenosine A2a receptors most likely facilitate release of an unknown inhibitory neurotransmitter, which, in turn, inhibits the CCR. We hypothesized that adenosine A2a receptors inhibit the CCR via facilitation of GABA release in the NTS. In urethane-chloralose-anesthetized rats (n = 51), we compared regional sympathetic responses evoked by stimulation of the CCR with right atrial injections of the 5-HT3 receptor agonist phenylbiguanide (1-8 μg/kg) before and after selective stimulation of NTS adenosine A2a receptors [microinjections into the NTS of CGS-21680 (20 pmol/50 nl)] preceded by blockade of GABAA or GABAB receptors in the NTS [bicuculline (10 pmol/100 nl) or SCH-50911 (1 nmol/100 nl)]. Blockade of GABAA receptors virtually abolished adenosine A2a receptor-mediated inhibition of the CCR. GABAB receptors had much weaker but significant effects. These effects were similar for the different sympathetic outputs. We conclude that stimulation of NTS adenosine A2a receptors inhibits CCR-evoked hemodynamic and regional sympathetic reflex responses via a GABA-ergic mechanism.
(Copyright © 2015 the American Physiological Society.)

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HL-67814 United States HL NHLBI NIH HHS

Keywords: adrenal nerve; lumbar nerve; nucleus of the solitary tract; purinergic receptors; renal nerve; γ-aminobutyric acid

0 ((+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid)
0 (Adenosine A2 Receptor Agonists)
0 (Biguanides)
0 (GABA Antagonists)
0 (Morpholines)
0 (Phenethylamines)
0 (Receptor, Adenosine A2A)
0 (Receptors, GABA-A)
0 (Receptors, GABA-B)
0 (Serotonin Receptor Agonists)
120225-54-9 (2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine)
K72T3FS567 (Adenosine)
W8PKA3T2I3 (phenyl biguanide)
Y37615DVKC (Bicuculline)

Date Created: 20150426 Date Completed: 20150915 Latest Revision: 20200930

20240628

PMC4491516

10.1152/ajpheart.00838.2014

25910812