ArticleBritish journal of pharmacology1996
Discrimination by PPADS between endothelial P2Y- and P2U-purinoceptors in the rat isolated mesenteric arterial bed.
Article in British journal of pharmacology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 71 citations in OpenAlex.
- P2Y₂ receptor activation decreases blood pressure via intermediate conductance potassium channels and connexin 37.Acta physiologica (Oxford, England) · 2015Article
- P2Y receptors in the mammalian nervous system: pharmacology, ligands and therapeutic potential.CNS & neurological disorders drug targets · 2012Review
- P2Y₂ receptor activation decreases blood pressure and increases renal Na⁺ excretion.American journal of physiology. Regulatory, integrative and comparative physiology · 2011Article
- Dinucleoside polyphosphates: strong endogenous agonists of the purinergic system.British journal of pharmacology · 2009Review
- Mechanism of ATP-induced local and conducted vasomotor responses in isolated rat cerebral penetrating arterioles.Journal of vascular research · 2009Article
- P2Y(1) and P2Y(2) receptors are coupled to the NO/cGMP pathway to vasodilate the rat arterial mesenteric bed.British journal of pharmacology · 2002Article
- The involvement of smooth muscle P2X receptors in the prolonged vasorelaxation response to purine nucleotides in the rat mesenteric arterial bed.British journal of pharmacology · 2002Article
- Structure-activity relationships of diadenosine polyphosphates (Ap(n)As), adenosine polyphospho guanosines (Ap(n)Gs) and guanosine polyphospho guanosines (Gp(n)Gs) at P2 receptors in the rat mesenteric arterial bed.British journal of pharmacology · 2001Article
- Mechanism of prolonged vasorelaxation to ATP in the rat isolated mesenteric arterial bed.British journal of pharmacology · 2001Article
- The pharmacology of nucleotide receptors on primary rat brain endothelial cells grown on a biological extracellular matrix: effects on intracellular calcium concentration.British journal of pharmacology · 2000Article
- The stable pyrimidines UDPbetaS and UTPgammaS discriminate between the P2 receptors that mediate vascular contraction and relaxation of the rat mesenteric artery.British journal of pharmacology · 2000Article
- Evidence that rat hepatocytes co-express functional P2Y1 and P2Y2 receptors.British journal of pharmacology · 2000Article
- Extracellular nucleotide signaling in the inner ear.Molecular neurobiology · 1998Review
- P2 receptor excitation of rodent hypoglossal motoneuron activity in vitro and in vivo: a molecular physiological analysis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1997Article
- Inhibition of ecto-ATPase by PPADS, suramin and reactive blue in endothelial cells, C6 glioma cells and RAW 264.7 macrophages.British journal of pharmacology · 1996Article
- Cloned and transfected P2Y4 receptors: characterization of a suramin and PPADS-insensitive response to UTP.British journal of pharmacology · 1996Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. The main aim of this study was to characterize the antagonistic effects of pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) at coexisting endothelial P2Y- and P2U-purinoceptors. Studies were conducted in Krebs-perfused mesenteric arterial preparations isolated from the rat, with tone raised by methoxamine (5-50 microM). 2. Purine and pyrimidine compounds elicited vasodilatation with a rank order of potency of 2-methylthio ATP (2-MeSATP) = ADP > ATP = UTP > P1, P3-diadenosine triphosphate (Ap3A) > P1, P2-diadenosine pyrophosphate (Ap2A) > NADP > adenosine. 8-para-Sulphophenyltheophylline (8-PSPT; 3 microM) had no effect on vasodilator responses to 2MeSATP, ADP, ATP, UTP, Ap3A or NADP, but blocked responses to adenosine and the maximal response to Ap2A. 3. PPADS (3-100 microM) attenuated vasodilator responses to the P2Y-selective agonists 2MeSATP and ADP, shifting the dose-response curves to the right. The pA2 values for PPADS at 2MeSATP and ADP were 5.97 +/- 0.69 and 5.98 +/- 0.86 respectively. In contrast, PPADS had no effect on vasodilator responses mediated by the P2U-selective agonist, UTP, or on vasodilator responses mediated by ATP. 4. PPADS (10 microM) was used to characterize responses mediated by the adenine dinucleotides; dose-response curves for vasodilator responses to Ap3A and NADP, but not those to Ap2A, were shifted to the right by PPADS. The estimated pA2 values for the effect of PPADS on Ap3A and NADP were 6.38 and 6.26 respectively. 5. Indomethacin (10 microM) had no effect on vasodilator responses to 2MeSATP, ADP, ATP or UTP. 6. In conclusion, these results show that PPADS is an antagonist at endothelial P2Y- but not P2U-purinoceptors in rat mesenteric arteries. These receptors cannot be discriminated by inhibition of prostaglandin synthesis; P2Y-purinoceptors are, however, sensitive to ADP. Selective antagonism by use of PPADS showed that ATP acts at P2U- and not P2Y-purinoceptors. Ap3A and NADP mediate vasodilatation via P2Y-purinoceptors, whereas vasodilatation to Ap2A is mediated partly via P1- and possibly via P2U-purinoceptors.
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