1 Adenosine-5'-triphosphate (ATP) is a potent coronary vasodilator. Because
of the efficient hydrolysis of ATP, adenosine-5'-diphosphate (ADP) and ade
nosine-5'-monophosphate (AMP) by ectonucleotidases located in the coronary
endothelium ATP-induced vasodilation may be mediated via both P1 (AMP and a
denosine) and P2Y (ATP and ADP) receptors. We have used the change in total
coronary resistance (TCR) induced by intravascular ATP in the isolated wor
king rat heart to determine both the component of the vasodilation mediated
via P2Y receptors and the identity of the subclass of receptor involved.
2 The dose response for ATP revealed a half maximal effect at an apparent A
TP concentration of 0.08 +/- 0.009 mu M. The response was saturated at appa
rent ATP concentrations greater than 0.23 mu M. Contrary to much of the cur
rent literature, the perfusion of a 0.25 mu M concentration of adenosine re
sulted in the identical response to an equimolar concentration of ATP sugge
sting a significant role for adenosine in coronary vasodilation.
3 The non-selective P1 receptor antagonist 8-(p-Sulfophenyl)theophylline (8
-SPT) was used to show that the response to ATP was mediated via both P1 an
d P2Y receptors. Whilst 8-SPT abolished the effect of adenosine it reduced
the effect of ATP by only 50%. Thus, at a saturating concentration of ATP,
P1 and P2Y receptors were shown to contribute equally to the observed vasod
ilation.
4 Uridine-5'-triphosphate (UTP), ADP and adenosine-5'-O-thiotriphosphate (A
TP gamma S) were used to characterize the component of coronary vasodilatio
n that was mediated via P2Y receptors. UTP at 0.25 mu M was ineffective and
did not induce vasodilation. Perfusion with 0.25 mu M ADP resulted in a va
sodilation that was identical to 0.25 mu M ATP. In the absence of 8-SPT the
perfusion of 0.25 mu M ATP gamma S produced a vasodilation that was signif
icantly (P<0.05) less than ATP. However, the vasodilation due to ATP gamma
S, like that of adenosine, but unlike that of both ATP and ADP, was abolish
ed in the presence of 8-SPT. The ability of ADP to induce vasodilation comb
ined with both the lack of response to UTP and the ability of 8-SPT to abol
ish the vasodilation induced by ATP gamma S suggested very strongly that th
e component of ATP-induced coronary vasodilation in the isolated working ra
t heart that was mediated Pia P2Y receptors was achieved by the action of A
DP (and not ATP) at P2Y(1) receptors.
5 These results suggest that the vasodilatory action of intravascular ATP i
n the coronary circulation should be attributed to the dual and equal activ
ities of adenosine and ADP acting at P1 and P2Y(1) receptors respectively.