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Facilitation of noradrenaline release by activation of adenosine A(2A) receptors triggers both phospholipase C and adenylate cyclase pathways in rat tail artery.

Abstract：

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 [(3)H]-noradrenaline (0.1 microM), 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 microM), 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 microM). The PKC activator phorbol 12-myristate 13-acetate (PMA; 1 microM) 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.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Fresco P,Diniz C,Gonçalves J

doi

10.1016/j.cardiores.2004.05.015

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

739-46

issue

eissn

0008-6363

issn

1755-3245

pii

S0008636304002378

journal_volume

pub_type

杂志文章

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Facilitation of noradrenaline release by activation of adenosine A(2A) receptors triggers both phospholipase C and adenylate cyclase pathways in rat tail artery.