1 In this study the regulation of cardiac sympathetic outflow by presynapti
c P-2X receptor-gated ion channels was examined.
2 ATP (30 muM-1 mM) and other P2-receptor agonists elicited [H-3]-noradrena
line ([H-3]-NA) outflow from the isolated guinea-pig right atrium with the
potency order of ATP>2-methylthioATP > alpha,beta -methylene-ATP = ADP, whe
reas beta,gamma -methylene-L-ATP was inactive.
3 Ca2+-free conditions abolished both electrical field stimulation (EFS)- a
nd ATP-evoked release of tritium. Unlike from EFS-induced outflow, ATP-indu
ced [SH]-NA outflow was not reduced by omega -Conotoxin-GVIA (100 nM), Cd2 (100 muM) and tetrodotoxin (1 muM).
4 The rapid extracellular decomposition of ATP was revealed by HPLC analysi
s. However, the effect of ATP to promote [H-3]-NA release was not prevented
by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 250 nM), 3,7-dimethyl-1-prop
argylxanthine (DMPX, 250 nM), or by reactive blue 2 (RB2, 10 muM), antagoni
sts of A(1)-, A(2)- and inhibitory P-2 receptors.
5 Zn2+ (50 muM), the P-2X-receptor modulator potentiated, and P-2X receptor
antagonists, i.e. suramin (300 muM), pyridoxal-phosphate-6-azophenyl-2',4'
-disulphonic acid (PPADS, 30 muM) and 2'-o-(trinitrophenyl)-adenosine 5'-tr
iphosphate (TNP-ATP, 30 muM) antagonized the ATP (1 mM)-evoked response.
6 RT-PCR study revealed the expression of P-2X2 and P-2X3 receptor mRNAs in
guinea-pig superior cervical ganglion.
7 PPADS (30 muM) significantly reduced the EFS-induced [H-3]-NA outflow in
the presence DPCPX (250 nM) and RB2 (10 muM).
8 In summary a P-2X-type purinoceptor regulates noradrenaline release from
the isolated right atrium of the guinea-pig. The pharmacological profile of
the receptor resemble to homo-oligomeric P-2X3 Or hetero-oligomeric P-2X2/
P-2X3 complexes, and provide a new target to intervene on sympathetic neuro
effector transmission at the presynaptic site.