Effects of P1 and P2Y purinoceptor antagonists on endothelium-dependent and -independent relaxations of rat mesenteric artery to GTP and guanosine.
1. Guanosine 5'-triphosphate (GTP) and guanosine can relax both endothelium-intact and -denuded arterial preparations. In the present work the P1 and P2Y purinoceptor antagonists, 8-phenyltheophylline and reactive blue 2, respectively, were used to study the mechanisms of relaxation responses induced by GTP, guanosine, adenosine 5'-triphosphate (ATP) and adenosine in noradrenaline-precontracted rat mesenteric artery rings. 2. GTP (10 microM-1mM) dose-dependently relaxed endothelium-intact mesenteric artery rings and also induced moderate relaxation responses in endothelium-denuded preparations. Pretreatment of the rings with 8-phenyltheophylline (10 microM) or reactive blue 2 (10 microM) did not attenuate the relaxant effect of GTP. 3. Guanosine (10 microM-1mM) relaxed both endothelium-intact and -denuded artery rings in a dose-dependent manner. The presence of 8-phenyltheophylline or reactive blue 2 had no effects on guanosine-induced relaxations. 4. ATP-induced (0.1 microM-0.1 mM) relaxation of endothelium-intact artery rings was attenuated by reactive blue 2 while 8-phenyltheophylline was ineffective. ATP also relaxed endothelium-denuded artery rings and this relaxation was inhibited by 8-phenyltheophylline, but not by reactive blue 2. 5. Adenosine-induced (10 microM-1 mM) relaxation of endothelium-intact and -denuded artery rings was attenuated by the presence of 8-phenyltheophylline, but not of reactive blue 2. 6. In conclusion, the endothelium-dependent and -independent relaxations of rat mesenteric arteries to GTP and guanosine are not mediated via P1 and P2Y purinoceptors. Therefore, these results support our previous suggestion on the presence of a novel guanine nucleotide-specific receptor, a putative PG receptor, on both endothelial and smooth muscle cells, which may participate in the regulation of arterial tone.
Department of Clinical Microbiology, Tampere University Hospital, Finland.
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Vuorinen
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Wu
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Arvola
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Vapaatalo
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Pörsti
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology*; D006151:Guanosine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology
D011500:Protein Synthesis Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D014227:Triazines; D006151:Guanosine; C012842:Cibacron Blue F 3GA; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine