Facilitation of noradrenaline release by activation of adenosine A_2A receptors triggers both phospholipase C and adenylate cyclase pathways in rat tail artery

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• 作者：Fresco ; Paula ; Diniz ; Carmen ; Gonç ; alves ; Jorge
• 关键词：Adenosine ; Receptors ; Protein kinase C ; Protein kinase A ; Signal transduction
• 刊名：Cardiovascular Research
• 出版年：2004
• 出版时间：September 1, 2004
• 年：2004
• 卷：63
• 期：4
• 页码：739-746
• 全文大小：295 K

文摘

Objective: The present work is aimed at elucidating the signalling pathway(s) triggered by activation of A_2A receptors involved in the facilitation of noradrenaline release in rat tail artery as an attempt to clarify their role in the cardiovascular system. Methods: Electrically evoked (5 Hz, 100 pulses, 1 ms) tritium overflow was evaluated in preparations of rat tail artery, pre-incubated with [³H]-noradrenaline (0.1 56;M), in the absence or in the presence of adenosine receptor agonists and antagonists and/or activators and inhibitors of phospholipase C (PLC)-protein kinase C (PKC) and of adenylate cyclase (AC)-cyclic adenosine-3′,5′-monophosphate (cAMP)-protein kinase A (PKA) pathways. Results: Activation of A_2A receptors by 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine (CGS 21680; 100 nM) enhanced tritium overflow, an effect prevented by the A_2A receptor antagonist 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo-[4,3]-1,2,4-triazolo[1,5]pyrimidine (SCH 58261; 20 nM), by the protein kinase A (PKA) inhibitor N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide (H-89; 1 56;M), or the PKC inhibitor 2-(8-[(dimethylamino)methyl-6,7,8,9-tetrahydropyrido[1,2]indol-3-yl]-3-(1-methylindol-3-yl)maleimide (Ro 32-0432; 1 56;M). The PKC activator phorbol 12-myristate 13-acetate (PMA; 1 56;M) and the PKA activator 8-bromo-cAMP (0.5 mM) also enhanced tritium overflow. The effect caused by PMA was blunted both by Ro 32-0432 and by H-89 whereas that caused by 8-bromo-cAMP was only prevented by H-89. Conclusions: In rat tail artery, the A_2A receptor-mediated facilitation of noradrenaline release requires activation of both PKC and PKA, and PKA activation seems to occur downstream of PKC activation.