title: The role of intraspinal adenosine A1 receptors in sympathetic regulation.
abstract: Using a splanchnic nerve-spinal cord preparation in vitro, we have previously demonstrated that tonic sympathetic activity is generated from the thoracic spinal cord. Here, we sought to determine if adenosine receptors play a role in modulating this spinally generated sympathetic activity. Various adenosine analogs were applied. N6-Cyclopentyladenosine (CPA, adenosine A1 receptor agonist) and 5'-N-ethylcarboxamidoadenosine (NECA, adenosine A1/A2 receptor agonist) reduced, while N6-[2-(4-aminophenyl)ethyl]adenosine (APNEA, non-selective adenosine A3 receptor agonist) did not alter sympathetic activity. The inhibitory effect of CPA or NECA on sympathetic activity was reversed by 8-cyclopentyltheophylline (CPT, adenosine A1 receptor antagonist) or abolished by CPT pretreatment. In the presence of 3,7-dimethyl-1-propargylxanthine (DMPX, adenosine A2 receptor antagonist), sympathetic activity was still reduced by CPA or NECA. Sympathetic activities were not changed by applications of the more selective adenosine A2 or A3 receptor agonists or antagonists, including 4-[2-[[6-amino-9-(N-ethyl-beta-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid (CGS21680), 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385), 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Chloro-IB-MECA), and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS1191). These findings exclude a possible involvement of A2 or A3 receptors in sympathetic regulation at the spinal levels. Interestingly, CPT alone did not affect sympathetic activity, suggesting that adenosine A1 receptors are endogenously quiescent under our experimental conditions. We conclude that intraspinal adenosine A1 receptors may down-regulate sympathetic outflow and serve as a part of the scheme for neuroprotection.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taiwan.
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Peng
authors.forename: Chiu-Ming
authors.initials: CM
authors.lastname: Ho
authors.forename: Shung-Tai
authors.initials: ST
authors.lastname: Ho
authors.forename: Shen-Kou
authors.initials: SK
authors.lastname: Tsai
authors.forename: Chun-Kuei
authors.initials: CK
authors.lastname: Su
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D058909:Adenosine A3 Receptor Agonists; D058918:Adenosine A3 Receptor Antagonists; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D004095:Dihydropyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013153:Splanchnic Nerves / Q000187:drug effects / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D013805:Theobromine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D058909:Adenosine A3 Receptor Agonists; D058918:Adenosine A3 Receptor Antagonists; D004095:Dihydropyridines; C107728:MRS 1191; D043682:Receptor, Adenosine A1; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C055488:8-cyclopropyltheophylline; C053907:8-cyclopentyl-1,3-dimethylxanthine; D019830:Adenosine-5'-(N-ethylcarboxamide); C048599:N(6)-cyclopentyladenosine; C057837:3,7-dimethyl-1-propargylxanthine; D013806:Theophylline; D000241:Adenosine; D013805:Theobromine