The stable pyrimidines UDP beta S and UTP gamma S discriminate between theP2 receptors that mediate vascular contraction and relaxation of the rat mesenteric artery
M. Malmsjo et al., The stable pyrimidines UDP beta S and UTP gamma S discriminate between theP2 receptors that mediate vascular contraction and relaxation of the rat mesenteric artery, BR J PHARM, 131(1), 2000, pp. 51-56
1 The contractile and relaxant effects of the different P2 receptors were c
haracterized in the rat isolated mesenteric artery by use of extracellular
nucleotides, including the stable pyrimidines uridine 5'-O-thiodiphosphate
(UDP beta S) and uridine 5'-O-3-thiotriphosphate (UTP gamma S).
2 The selective P2X receptor agonist, alpha beta-methylene-adenosine tripho
sphate (alpha beta-MeATP) stimulated a potent (pEC(50)=6.0) but relatively
weak contraction (E-max=57% of 60 mM K+). The contractile concentration-res
ponse curve of adenosine triphosphate (ATP) was biphasic when added in sing
le concentrations. The first part of the response could be desensitized by
alpha beta-MeATP, indicating involvement of P2X receptors, while the second
part might be mediated by P2Y receptors.
3 The contractile P2Y receptors were further characterized after P2X recept
or desensitization with 10 mu M alpha beta-MeATP. Uridine diphosphate (UDP)
, uridine triphosphate (UTP) and ATP stimulated contraction only in high co
ncentrations (1-10 mh I). The selective P2Y(6) agonist, UDP beta S, and the
P2Y(2)/P2Y(4)-receptor agonists UTP gamma S and adenosine 5'-O-3-thiotriph
osphate (ATP gamma S) were considerably more potent and efficacious (E(max)
approximate to 250% of 60 mM K+). Adenosine 5'-O-thiodiphosphate (ADP beta
S) was inactive, excluding contractile P2Y, receptors.
4 After precontraction with 1 mu M noradrenaline, UTP, ADP and ATP induced
relaxations with similar potencies (pEC(50)approximate to 5.0). UTP gamma S
, ADP beta S and ATP gamma S were approximately one log unit more potent in
dicating the presence of endothelial P2Y(1) and P2Y(2)/P2Y(4) receptors. Th
e P2Y(6) receptor agonist, UDP beta S, had no effect.
5 UDP beta S and UTP gamma S are useful tools when studying P2 receptors in
tissue preparations with ectonucleotidase activity. Contractile responses
can be elicited by stimulation of P2Y(6) and, slightly less potently, P2Y(2
)/P2Y(4) receptors. The P2X response was relatively weak, and there was no
P2Y(1) response. Stimulation of P2Y(1) and P2Y(2)/P2Y(4) receptors elicited
relaxation, while P2Y, did not contribute.