The effect of PPADS as an antagonist of inositol (1,4,5)trisphosphate induced intracellular calcium mobilization

Vigne, Paul; Pacaud, Pierre; Urbach, V.; Feolde, Erick; Breittmayer, Jean‐Philippe; Frelin, Christian

doi:10.1111/j.1476-5381.1996.tb15994.x

Cited by 27 publications

(18 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This drug has been shown to act as a potent antagonist of P 2X receptors, and also, with a lower potency, as an antagonist of P 2Y receptors (for review see [30]). This compound has been reported to block the P 2Y receptor-mediated, ATP-induced intracellular Ca 2+ mobilization by a non-specific mechanism that probably involves the inhibition of inositol-1,4,5-trisphosphate (InsP 3 ) channels [46]. RB-2, a selectively P 2Y subtype antagonist [7], was most effective at inhibiting ATP-dependent [Ca 2+ ] i increases in pituicytes.…”

Section: Discussionmentioning

confidence: 99%

ATP acting on P 2Y receptors triggers calcium mobilization in primary cultures of rat neurohypophysial astrocytes (pituicytes)

Troadec¹,

Thirion²,

Petturiti³

et al. 1999

Pfl�gers Archiv European Journal of Physiology

View full text Add to dashboard Cite

The effect of adenosine triphosphate (ATP) on the intracellular Ca2+ concentration ([Ca2+]i) of cultured neurohypophysial astrocytes (pituicytes) was studied by fluorescence videomicroscopy. ATP evoked a [Ca2+]i increase, which was dose dependent in the 2.5-50 microM range (EC50=4.3 microM). The ATP-evoked [Ca2+]i rise was not modified during the first minute following the removal of external Ca2+. Application of 500 nM thapsigargin inhibited the ATP-dependent [Ca2+]i increase. Caffeine (10 mM) and ryanodine (1 microM) did not affect the ATP-induced [Ca2+]i rise. The pituicytes responded to various P2 purinoceptor agonists with the following order of potency: ATP=ATP[gamma-S]=2-MeSATP>/=ADP, where ATP[gamma-S] is adenosine 5'-O-(3-thiotriphosphate) and 2-MeSATP is 2-methylthio-adenosine-5'-triphosphate. Adenosine, AMP, alpha, beta-methylene adenosine-5'-triphosphate (alpha,beta-MeATP), beta, gamma methylene adenosine-5'-triphosphate (beta,gamma-MeATP) and uridine 5'-triphosphate (UTP) were ineffective. The P2 purinoceptor antagonists blocked the ATP-evoked [Ca2+]i increase with the following selectivity: RB-2>suramin>PPADS, where RB-2 is Reactive Blue 2 and PPADS is pyridoxal-phosphate-6-azophenyl-2', 4'-disulphonic acid. The ATP-evoked [Ca2+]i increase was substantially blocked by pertussis toxin treatment, suggesting that it might be mediated by a pertussis-toxin-sensitive G protein. The phospholipase C (PLC) inhibitor U-73122 (0.5 microM) abolished the ATP-evoked [Ca2+]i rise, whereas its inactive stereoisomer U-73343 (0.5 microM) remained ineffective. Our results indicate that, in rat cultured pituicytes, ATP stimulation induces an increase in [Ca2+]i due to PLC-mediated release from intracellular stores through activation of a pertussis-toxin-sensitive, G-protein-linked P2Y receptor.

show abstract

Section: Discussionmentioning

confidence: 99%

ATP acting on P 2Y receptors triggers calcium mobilization in primary cultures of rat neurohypophysial astrocytes (pituicytes)

Troadec¹,

Thirion²,

Petturiti³

et al. 1999

Pfl�gers Archiv European Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…It is thought that neither cell death (Chan and Lin-Shiau, 2001) nor unspecific effects of PPADS such as the inhibition of ectonucleotidase activity (Windscheif et al, 1995) or the inhibition of IP 3 -induced Ca 2+ mobilization by a nonspecific mechanism (Vigne et al, 1996) contribute to the PPADS-mediated effects at the tested dose. Furthermore, it should be emphasized that in contrast to the P2 receptor antagonists suramin and reactive blue 2 no direct glutamate antagonistic properties were found for PPADS (Fröhlich et al, 1996;Motin and Bennett 1995;Gu et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Stimulation of P2Y1 Receptors Causes Anxiolytic-like Effects in the Rat Elevated Plus-maze: Implications for the Involvement of P2Y1 Receptor-Mediated Nitric Oxide Production

Kittner

Franke

Fischer

et al. 2002

Neuropsychopharmacol

View full text Add to dashboard Cite

(ADPbS), the P2X 1,3 receptor agonist a,b-methylene ATP (a,bmeATP), the unspecific P2 receptor antagonist pyridoxalphosphate-6-azopheny l-2 0 ,4 0 -disulfonic acid (PPADS), and the specific P2Y 1 receptor antagonist N 6 -methyl-2 0 -deoxyadenosine-3 0 ,5 0 -bisphosphate (MRS 2179) on the elevated plus-maze behavior of the rat were investigated. All tested compounds were given intracerebroventricularly (0.5 ml). ADPbS (50 and 500 fmol) produced an anxiolytic-like behavioral profile reflected by an increase of the open arm exploration. The anxiolytic-like effects were antagonized by pretreatment with PPADS (5 pmol) or MRS 2179 (5 pmol). Both compounds caused anxiogenic-like effects when given alone. Furthermore, the anxiolytic-like effects of ADPbS could be antagonized by pretreatment with the nitric oxide synthase (NOS) inhibitor N w -nitro-L-arginine methyl ester (L-NAME). In addition, the anxiogenic-like effects of PPADS were reversed by the pretreatment with L-arginine (500 pmol), which is the natural substrate for NOS, but not by D-arginine (500 pmol), which is not. Immunofluorescence staining revealed the presence of P2Y 1 receptors on neurons in different brain regions such as hypothalamus, amygdala, hippocampus and the periaqueductal gray. Furthermore, the colocalization of P2Y 1 receptors and neuronal NOS (nNOS) on some neurons in these regions could be demonstrated. The highest density of P2Y 1 -and nNOS-immunoreactivity was detected in the dorsomedial hypothalamic nucleus. Taken together, the present results suggest that P2Y 1 receptors are involved in the modulation of anxiety in the rat. The anxiolytic-like effects after stimulation of P2Y 1 receptors seem to be in close connection with the related nitric oxide production.

show abstract

“…A possible non-specific action of PPADS (cf. McLaren et al 1994;Vigne et al 1996) is not likely to contribute to the above interaction. PPADS is able to inhibit the relaxant action of exogenous ATP in the guineapig taenia caeci (Windscheif et al 1995;Barthó et al 1998).…”

Section: Discussionmentioning

confidence: 86%

Inhibitory effect of PACAP(6-38) on relaxations induced by PACAP, VIP and non-adrenergic, non-cholinergic nerve stimulation in the guinea-pig taenia caeci

Lénárd

Lázár

Benkó

et al. 2000

Naunyn-Schmiedeberg's Archives of Pharmacology

View full text Add to dashboard Cite

The effect of the pituitary adenylate cyclase activating polypeptide (PACAP) receptor antagonist PACAP(6-38) on the relaxant response to exogenous PACAP, vasoactive intestinal polypeptide (VIP) and nonadrenergic, non-cholinergic (NANC) nerve stimulation was tested in the guinea-pig taenia caeci, in the presence of atropine (10(-6) M) and guanethidine (3x10(-6) M). PACAP(6-38) (3x10(-6) M) strongly inhibited sub-maximal relaxations evoked by exogenous PACAP (1-3x 10(-8) M) or VIP (10(-8) M), but not those due to isoprenaline (4-8x10(-8) M) or ATP (10(-6) M). PACAP(6-38) caused a small but significant (approximately 20%) inhibition of the NANC relaxation due to electrical field stimulation (1 Hz or 10 Hz for 20 s). At these frequencies PACAP(6-38) caused no inhibition of the NANC relaxation in the presence of the P2 purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 5x10(-5) M), or PPADS plus the NO-synthase blocker NG-nitro-L-arginine (L-NOARG; 10(-4) M); in preparations pretreated with L-NOARG (10(-4) M) alone PACAP(6-38) retained its inhibitory effect. The PPADS- and L-NOARG-resistant NANC relaxation with 10 Hz electrical stimulation was blocked by apamin (10(-7) M); it was not significantly modified by the tachykinin receptor antagonist spantide (10(-5) M). Tachyphylaxis to PACAP(1-27) (10(-7) M for 10 min) strongly inhibited the relaxation due to PACAP(1-38) (1-3x10(-8) M) and reduced electrical stimulation-evoked relaxations by half. The putative VIP antagonist VIP(10-28) (10(-5) M) failed to significantly reduce the relaxant action of exogenous VIP (1-3x10(-8) M). Relaxation induced by PACAP(1-38) (1-2x10(-8) M) was not influenced by a mixture of PPADS (5x10(-5) M) and L-NOARG (10(-4) M). It is concluded that: (a) PACAP(6-38) is a VIP/PACAP antagonist in the guinea-pig taenia caeci; (b) a release of a VIP/PACAP-like substance from enteric nerves is involved in the NANC relaxation in this preparation, but its contribution is relatively small and seems to depend on the functional integrity of the PPADS-sensitive inhibitory mechanism; (c) the PPADS- plus L-NOARG-resistant NANC relaxation probably involves apamin-sensitive K+ channels.

show abstract

The effect of PPADS as an antagonist of inositol (1,4,5)trisphosphate induced intracellular calcium mobilization

Abstract: 6 It is concluded that PPADS does not recognize rat P2Y2-purinoceptors and prevents UTP and ATP induced intracellular Ca2+ mobilization by a non-specific mechanism that could involve the inhibition of InsP3 channels.

Cited by 27 publications

References 14 publications

ATP acting on P 2Y receptors triggers calcium mobilization in primary cultures of rat neurohypophysial astrocytes (pituicytes)

ATP acting on P 2Y receptors triggers calcium mobilization in primary cultures of rat neurohypophysial astrocytes (pituicytes)

Stimulation of P2Y1 Receptors Causes Anxiolytic-like Effects in the Rat Elevated Plus-maze: Implications for the Involvement of P2Y1 Receptor-Mediated Nitric Oxide Production

Inhibitory effect of PACAP(6-38) on relaxations induced by PACAP, VIP and non-adrenergic, non-cholinergic nerve stimulation in the guinea-pig taenia caeci

Contact Info

Product

Resources

About