Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P2Y- and facilitatory A2A-purinoceptors.
1. The effects of analogues of adenosine and ATP on noradrenaline release elicited by electrical stimulation (5 Hz, 2700 pulses) were studied in superfused preparations of rat tail artery. The effects of purinoceptor antagonists, of adenosine deaminase and of adenosine uptake blockade were also examined. Noradrenaline was measured by h.p.l.c. electrochemical detection. 2. The A1-adenosine receptor agonist, N6-cyclopentyladenosine (CPA; 0.1-100 nM) reduced, whereas the A2A-receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 3-30 nM) increased evoked noradrenaline overflow. These effects were antagonized by the A1-adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 20 nM) and the A2-adenosine receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX; 100 nM), respectively. The P2Y-purinoceptor agonist, 2-methylthio-ATP (1-100 microM) reduced noradrenaline overflow, an effect prevented by the P2-purinoceptor antagonist, cibacron blue 3GA (100 microM) and suramin (100 microM). 3. Adenosine deaminase (2 u ml-1), DMPX (100 nM) and inhibition of adenosine uptake with S-(p-nitrobenzyl)-6-thioinosine (NBTI; 50 nM) decreased evoked noradrenaline overflow. DPCPX alone did not change noradrenaline overflow but prevented the inhibition caused by NBTI. The P2Y-purinoceptor antagonist, cibacron blue 3GA (100 microM) increased evoked noradrenaline overflow as did suramin, a non-selective P2-antagonist. 4. It is concluded that, in rat tail artery, inhibitory (A1 and P2Y) and facilitatory (A2A) purinoceptors are present and modulate noradrenaline release evoked by electrical stimulation. Endogenous purines tonically modulate noradrenaline release through activation of inhibitory P2Y and facilitatory A2A purinoceptors, whereas a tonic activation of inhibitory A1 purinoceptors seems to be prevented by adenosine uptake.
Gonçalves
J
J
Department of Pharmacology, University of Porto, Portugal.
Queiroz
G
G
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011983:Receptors, Purinergic / Q000187:drug effects*; D013623:Tail; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D010627:Phenethylamines; D011983:Receptors, Purinergic; D013873:Thionucleotides; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C048599:N(6)-cyclopentyladenosine; D013868:Thioinosine; D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000243:Adenosine Deaminase; C001789:4-nitrobenzylthioinosine; D000241:Adenosine; D009638:Norepinephrine; C008501:2-methylthio-ATP