Reactive blue 2 discriminates between responses mediated by UTP and those evoked by ATP or α, β-methylene-ATP on rat sympathetic ganglia

Connolly, G.P.; Harrison, P J

doi:10.1016/0014-2999(94)90165-1

Cited by 21 publications

(15 citation statements)

References 13 publications

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“…and ATPyS. We have reported that other P2-purinoceptor antagonists such as reactive blue 2 and PPADS enhanced the depolarization of the rat SCG evoked by UTP (Connolly & Harrison, 1994;Connolly, 1995). On the guineapig urinary bladder, reactive blue 2 at a concentration above that used in our studies (10 mM) did not inhibit ecto-5'-nucleotidase (Hourani & Chown, 1989).…”

Section: Methodscontrasting

confidence: 41%

“…ATP (see Table 1 Connolly & Harrison, 1994) or in the presence of 8-PT (a non selective P1-purinoceptor antagonist that antagonizes both Al-and A2-adenosine receptors) suggests that the receptors mediating the actions of UTP are unlikely to be P1-purinoceptors. Therefore, UTP must act via P2-purinoceptors, nucleotide or pyrimidinoceptors.…”

Section: Methodsmentioning

confidence: 99%

“…We recently reported that the effects of ATP and UTP on the rat superior cervical ganglion (SCG) may be mediated through purinoceptors and pyrimidinoceptors respectively (Connolly & Harrison, 1993). Our hypothesis was based upon the observations that the UTP-evoked depolarization was unaltered or enhanced in the presence of suramin , reactive blue 2 (Connolly & Harrison, 1994), the 2',4'-and 2',5'-disulphonic acid isomers of 6-azophenyl-pyridoxal-phosphate (PPADS and IsoPPADS) (Connolly, 1995) whereas these P2-purinoceptor antagonists decreased depolarizations evoked by a,fi-methylene-ATP (a,fi-MeATP) or ATP.…”

Section: Introductionmentioning

confidence: 99%

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Structure‐activity relationship of a pyrimidine receptor in the rat isolated superior cervical ganglion

Connolly

Harrison

1995

British J Pharmacology

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1 The effects of pyrimidines and purines on the d.c. potential of the rat isolated superior cervical ganglion (SCG) have been examined by a grease-gap technique to determine the structure-activity requirements of the receptor activated by pyrimidines, i.e. a pyrimidinoceptor. 2 5-Aminoimidazole4-carboxamide-l-f-D-ribofuranosyl (ZTP), the pyrimidines, cytidine 5'-triphosphate (CTP), uridine 5'-triphosphate (UTP) and thymidine 5'-triphosphate (TTP) and the purines, adenosine 5'-triphosphate (ATP; in the presence of an Al-purinoceptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (1 Mm)), adenosine 5'-0-(3-thiotriphosphate) (ATPyS), guanosine 5'-triphosphate (GTP), inosine 5'-triphosphate (ITP) depolarized ganglia in a concentration-dependent manner.The relative order of ZTP and purine 5'-triphosphates in depolarizing ganglia was ZTP>ATPyS > >ATP? ITP=GTP, and for the pyrimidine 5'-triphosphates UTP>TTP>CTP. Depolarizations evoked by ATPyS were followed by concentration-dependent hyperpolarizations at 100 and 1000 MM. 3 At concentrations of between 0.1 Mm and 1 mm, uridine 5'-diphosphate (UDP), uridine 5'-diphosphoglucose (UDPG) and uridine 5'-diphosphoglucuronic acid (UDPGA) evoked significant and concentration-dependent depolarizations, whereas uridine 5'-monophosphate (UMP), uridine and uracil were inactive or produced small (<45 pY) depolarizations. The relative order of potency of uridine analogues in depolarizing ganglia was UDP> UTP > UDPG > UDPGA > > uracil > UMP = pseudouridine uridine. At 3 and 10 mM, uridine produced concentration-dependent hyperpolarizations. Nikkomycin Z, a nucleoside resembling UTP (viz. the triphosphate chain at the 5'-position on the ribose moiety being replaced by a peptide), was inactive between 1 uM and 1 mM. Generally, a concentration of 10 mm was required before thymidine, 6-azathymine, 6-azauracil or 6-azauridine depolarized ganglia. 4 Suramin (300 Mm), a P2-purinoceptor antagonist, significantly depressed depolarizations evoked by a,fi-methylene-ATP (a,fi-MeATP; 100 Mm), ATPyS (100 Mm), CTP (1 mM), GTP (1 mM), ZTP (30 MM) and ATP (300 MM) in the presence of DPCPX (1 yM). Suramin reversed a small depolarization evoked by UMP (1 mM) into a small hyperpolarization. In contrast depolarizations evoked by UDP, UTP, UDPG (all at 100 Mm) and TTP (300 Mm) were unaltered or enhanced by suramin. 5 It is concluded that the rat SCG contains distinct nucleotide receptors including a P2-purinoceptor (activated by a,f,-MeATP, ATP, GTP, ITP and ZTP) and a pyrimidinoceptor (activated by UTP, UDP, UDPG, UDPGA and TTP). The pyrmidinoceptor on rat SCG neurones had specific structure activity requirements with the di-and triphosphates of uridine being the most effective depolarizing agonists examined.

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Section: Methodscontrasting

confidence: 41%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Structure‐activity relationship of a pyrimidine receptor in the rat isolated superior cervical ganglion

Connolly

Harrison

1995

British J Pharmacology

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“…Pyrimidinoceptors have been suggested to exist in rabbit basilar and ear, arteries (Von Kugelgen et al, 1987;Von Kugelgen & Starke, 1990), the perfused isolated liver of the rat , rat superior cervical ganglion (Connolly & Harrison, 1994), mouse neuroblastoma NG108-15 cells (Lin, 1994;Reiser, 1995), rat C6-2B glioma cells , HL-60 and neutrophils (Seifert & Schultz, 1989 cells (Lin, 1994;Reiser, 1995) and the PI and AA responses (to UDP) in C6-2B glioma cells UTP and UDP are much more potent than other nucleotide (Greenberg et al, 1988;El-Moatassim & Dubyak, 1992 T were used in this study to characterize pyrimidinoceptors. Suramin has been shown to be a competitive antagonist of P2 purinoceptors, but it does not appear to distinguish between the subtypes (Fredholm et al, 1994).…”

Section: Measurements Of Pi Turnovermentioning

confidence: 99%

“…Pyrimidinoceptors-that are activated specifically by UTP rather than ATP have been suggested to exist in rabbit basilar and ear arteries (Von Kugelgen et al, 1987; Kugelgen & Starke, 1990), the isolated perfused rat liver , rat sympathetic ganglia (Connolly & Harrison, 1994), NG108-15 neuroblastoma (Lin, 1994;Reiser, 1995) and C6-2B rat glioma cells .…”

Section: Introductionmentioning

confidence: 99%

Pyrimidinoceptor‐mediated activation of phospholipase C and phospholipase A₂ in RAW 264.7 macrophages

Lin

Lee

1996

British J Pharmacology

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Taiwan1 As well as the presence of P2Z purinoceptors previously found in macrophages, we identified pyrimidinoceptors in RAW 264.7 cells, which activate phospholipase C (PLC) and phospholipase A2 (PLA2).2 The relative potency of agonists to stimulate inositol phosphate (IP) formation and arachidonic acid (AA) release was UTP = UDP > > ATP, ATPyS, 2MeSATP. For both signalling pathways, the EC50 values for UTP and UDP (3 uiM) were significantly lower than that for ATP and all other analogues tested (> 100 yM).3 UTP and UDP displayed no additivity in terms of IP formation and AA release at maximally effective concentrations. 4 UTP-, but not ATP-, evoked AA release was 60% inhibited by pertussis toxin (PTX), while stimulation of IP formation by both agonists was unaffected. Short-term treatment with phorbol 12-myristate 13-acetate (PMA) led to a dose-dependent inhibition of IP responses to UTP and UDP, but failed to affect the AA responses. Removal of extracellular Ca2+ inhibited the PI response to UTP, but abolished its AA response. 5 ATP-induction of these two transmembrane signal pathways was decreased in high Mg2+-containing medium but potentiated by the removal of extracellular Mg2'. 6 Suramin and reactive blue displayed equal potency to inhibit the IP responses of UTP and ATP.7 Both UTP and UDP (0.1-100 pM) induced a sustained increase in [Ca21], which lasted for more than 10 min. 8 Taken together, these results indicate that in mouse RAW 264.7 macrophages, pyrimidinoceptors with specificity for UTP and UDP mediate the activation of PLC and cytosolic (c) PLA2. The activation of PLC is via a PTX-insensitive G protein, whereas that of cPLA2 is via a PTX-sensitive G proteindependent pathway. The sustained Ca2+ influx caused by UTP contributes to the activation of cPLA2.RAW 264.7 cells also possess P2z purinoceptors which mediate ATP4--induced PLC and PLA2 activation.

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P2 Purinoceptors and Pyrimidinoceptors of Catecholamine‐Producing Cells and Immunocytes

Illéš

Nieber

Fröhlich

et al. 2007

Ciba Foundation Symposium 198 ‐ P2 Purinoceptors: Localization, Function and Transduction Mechanisms

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Reactive blue 2 discriminates between responses mediated by UTP and those evoked by ATP or α, β-methylene-ATP on rat sympathetic ganglia

Cited by 21 publications

References 13 publications

Structure‐activity relationship of a pyrimidine receptor in the rat isolated superior cervical ganglion

Structure‐activity relationship of a pyrimidine receptor in the rat isolated superior cervical ganglion

Pyrimidinoceptor‐mediated activation of phospholipase C and phospholipase A₂ in RAW 264.7 macrophages

P2 Purinoceptors and Pyrimidinoceptors of Catecholamine‐Producing Cells and Immunocytes

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Reactive blue 2 discriminates between responses mediated by UTP and those evoked by ATP or α, β-methylene-ATP on rat sympathetic ganglia

Cited by 21 publications

References 13 publications

Structure‐activity relationship of a pyrimidine receptor in the rat isolated superior cervical ganglion

Structure‐activity relationship of a pyrimidine receptor in the rat isolated superior cervical ganglion

Pyrimidinoceptor‐mediated activation of phospholipase C and phospholipase A2 in RAW 264.7 macrophages

P2 Purinoceptors and Pyrimidinoceptors of Catecholamine‐Producing Cells and Immunocytes

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Pyrimidinoceptor‐mediated activation of phospholipase C and phospholipase A₂ in RAW 264.7 macrophages