Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P_2Y‐ and facilitatory A_2A‐purinoceptors

Abstract

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 A,-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 Aladenosine 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 gM) reduced noradrenaline overflow, an effect prevented by the P2-purinoceptor antagonist, cibacron blue 3GA (100 gM) and suramin (100 gM).3 Adenosine deaminase (2 u ml-1), DMPX (100 nM) and inhibition of adenosine uptake with S-(pnitrobenzyl)-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 gM) increased evoked noradrenaline overflow as did suramin, a nonselective P2-antagonist.4 It is concluded that, in rat tail artery, inhibitory (Al 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 Al purinoceptors seems to be prevented by adenosine uptake.

Role of Endogenous Adenosine as a Modulator of Syncope Induced During Tilt Testing

“…11 The activation of A1 receptors mediates cardiac depression through negative chronotropic, dromotropic, and inotropic effects 12 and diminishes blood vessel tone via the prejunctional inhibition of neurotransmitter release on the perivascular sympathetic 13 and capsaicin- sensitive sensory afferents. 14 A2 receptors are subdivided into A2A (high affinity) and A2B (low affinity) subtypes.…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…Differential modulation of NA and ATP release by a 2 -adrenoceptors has been reported (Brock and Tan, 2004). There is modulation of NA release from sympathetic nerves in rat tail artery by inhibitory P2Y 1 and P2Y 12 receptors and facilitatory A 2A receptors (Gonçalves and Queiroz, 1996;Fresco et al, 2007;Quintas et al, 2009). ET-1 inhibited NA and ATP release from sympathetic nerves in the rat tail artery, whereas high concentrations of ET-3 potentiated the release of both transmitters (Mutafova-Yambolieva and Westfall, 1998).…”

Adenosine‐mediated hypotension in in vivo guinea‐pig: receptors involved and role of NO

“…Moreover, a signi®cant role of A 1 receptors in the regulation of BP also appears to be linked to a prejunctional regulation of transmitter release, such as from perivascular sympathetic nerves (Goncalves & Queiroz, 1996) or capsaicin-sensitive sensory neurons (Rubino et al, 1993).…”