Discrimination by PPADS between endothelial P<sub>2Y</sub>‐ and P<sub>2U</sub>‐ purinoceptors in the rat isolated mesenteric arterial bed

Ralevic, Vera; Burnstock, Geoffrey

doi:10.1111/j.1476-5381.1996.tb15420.x

Cited by 69 publications

(51 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The moderately selective P2Y 1 agonists ADP and 2-MeS-ATP exhibited response maxima that were 35 to 45% lower than values determined for ATP and UTP. The EC 50 values measured for ADP and 2-MeS-ATP are consistent with the EC 50 values for P2Y 1 receptors measured in other mammalian tissues (Simon et al, 1995;Nicholas et al, 1996;Pacaud et al, 1996;Ralevic and Burnstock, 1996;Palmer et al, 1998). In addition, the ADP-or 2-MeS-ATP-induced increase in intracellular Ca 2ϩ was blocked by the pretreatment of P2Y 1 antagonist MRS-2179.…”

Section: Discussionsupporting

confidence: 73%

Evidence for Multiple P2Y Receptors in Trabecular Meshwork Cells

Crosson¹,

Yates²,

Bhat³

et al. 2004

J Pharmacol Exp Ther

View full text Add to dashboard Cite

The purpose of this study was to determine whether functional purinergic P2 receptors are present in trabecular meshwork cells. The human trabecular cell line HTM-3 and cultured bovine trabecular cells were used to assess the effects of P2 agonists on intracellular Ca 2ϩ levels, extracellular signal-regulated kinase (ERK1/2) activation, and P2Y receptor expression. ATP, UTP, ADP, and 2-methyl-thio-adenosine triphosphate (2-MeS-ATP) each produced a concentration-dependent increase in intracellular Ca 2ϩ in bovine trabecular cells and the HTM-3 cell line. The addition of UDP did not produce any detectable rise in intracellular Ca 2ϩ . Pretreatment with the P2Y 1 receptor antagonist 2Ј-deoxy-N 6 -methyladenosine-3Ј,5Ј-diphosphate (MRS-2179) blocked the ADP-and 2-MeS-ATP-induced rise in intracellular Ca 2ϩ . However, the ATP-or UTP-induced rise in intracellular Ca 2ϩ was not inhibited by MRS-2179 pretreatment. The addition of ADP, 2-MeS-ATP, ATP, or UTP were also found to activate the ERK1/2 signaling pathway. This activation of ERK1/2 was blocked by pretreatment with the mitogenactivated protein kinase kinase inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene (U-0126) or the protein kinase C inhibitor chelerythrine chloride, but not by MRS-2179. Analysis of mRNA from HTM-3 cells by reverse transcription-polymerase chain reaction revealed the expression of P2Y 1 , P2Y 4 , and P2Y 11 receptor subtypes. These data demonstrate that multiple P2Y receptors are present in trabecular cells. Our results are consistent with the idea that the mobilization of intracellular Ca 2ϩ results from the activation of P2Y 1 and P2Y 4 receptors, whereas the activation of the ERK1/2 pathway results from the activation of P2Y 4 receptors alone. However, a role for the P2Y 11 receptors in mobilization of Ca 2ϩ , or activation of the ERK1/2 pathway, cannot be discounted.

show abstract

Section: Discussionsupporting

confidence: 73%

Evidence for Multiple P2Y Receptors in Trabecular Meshwork Cells

Crosson¹,

Yates²,

Bhat³

et al. 2004

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…In blood vessels, P2X receptors are expressed principally on the vascular smooth muscle, and in rat mesenteric arteries the main subtype is P2X 1 (Ralevic & Burnstock, 1996;Lewis & Evans, 2000). An involvement of P2X receptors, therefore, implies that the endothelium is not crucial for prolonged relaxation to purines, consistent with earlier reports (Steinmetz et al, 2000;Ralevic, 2001;Ralevic et al, 2001).…”

Section: +supporting

confidence: 79%

“…Mesenteric beds were isolated and perfused, via the superior mesenteric artery, as described previously (Ralevic & Burnstock, 1996). Brie¯y, the abdomen was opened and the superior mesenteric artery exposed and cannulated with a hypodermic needle.…”

Section: Methodsmentioning

confidence: 99%

“…Contraction is mediated principally by smooth muscle P2X receptors and rapid relaxation by endothelial P2Y receptors (principally P2Y 2 -like receptors) (Ralevic & Burnstock, 1988;1996;. The mechanism of the prolonged relaxation response, which can be modulated by a variety of pharmacological agents (Ralevic, 2001;Stanford et al, 2001), is, however, controversial.…”

Section: Introductionmentioning

confidence: 99%

“…The principal subtype of P2X receptor in blood vessels is the P2X 1 receptor, expressed on vascular smooth muscle (Ralevic & Burnstock, 1996;Lewis & Evans, 2000), so actions of a,bmeATP might seem to imply an involvement of the smooth muscle. Nonetheless, a possible involvement of the endothelium was investigated using sodium deoxycholate and distilled water treatment against responses to ATP, a,b-meATP, KCl and serotonin (5-HT).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The involvement of smooth muscle P2X receptors in the prolonged vasorelaxation response to purine nucleotides in the rat mesenteric arterial bed

Ralevic

2002

British J Pharmacology

View full text Add to dashboard Cite

1 ATP and adenine dinucleotides can elicit three dierent types of vasomotor response in the rat mesenteric arterial bed; vasocontraction, rapid relaxation (which may be masked by contraction) and slow and prolonged vasorelaxation. Contraction is mediated by smooth muscle P2X receptors and rapid relaxation by endothelial P2Y receptors. The mechanism of prolonged relaxation is, however, controversial. 2 In the present study, bolus injection of doses of a,b-methylene ATP (a,b-meATP; 5 pmol ± 0.5 mmol; P2X receptor agonist) in methoxamine-preconstricted rat isolated mesenteric arterial beds, mimicked the action of ATP, causing contraction (R max 76+9 mmHg) followed by prolonged relaxation (78+11%; t 1/2 14.6+1.5 min). KCl also elicited a biphasic response (R max contraction 73+8 mmHg; R max prolonged relaxation 70+6%; t 1/2 7.7+1.9 min). 3 P2X receptor desensitization caused by perfusion with a,b-meATP (10 mM) abolished contraction and prolonged relaxation to doses of a,b-meATP (50 nmol). Rapid relaxation (32+7%; t 1/2 32+2 s) was revealed, which was abolished by removal of the endothelium using distilled water. 4 Sodium deoxycholate treatment blocked contractile and prolonged relaxation responses to a,bmeATP, ATP and KCl, whilst distilled water treatment had no signi®cant eect on either phase of the biphasic responses. 5 These data indicate that smooth muscle P2X receptors are involved in both phases of the biphasic response (contraction followed by prolonged relaxation) to purine nucleotides in the rat isolated mesenteric arterial bed. Caution should be applied when using sodium deoxycholate to remove the endothelium because of possible damage caused by the detergent to receptors and/or the vascular smooth muscle.

show abstract

Dinucleoside Polyphosphates

Jankowski

2012

Uremic Toxins

View full text Add to dashboard Cite

Discrimination by PPADS between endothelial P_2Y‐ and P_2U‐ purinoceptors in the rat isolated mesenteric arterial bed

Cited by 69 publications

References 29 publications

Evidence for Multiple P2Y Receptors in Trabecular Meshwork Cells

Evidence for Multiple P2Y Receptors in Trabecular Meshwork Cells

The involvement of smooth muscle P2X receptors in the prolonged vasorelaxation response to purine nucleotides in the rat mesenteric arterial bed

Dinucleoside Polyphosphates

Contact Info

Product

Resources

About

Discrimination by PPADS between endothelial P2Y‐ and P2U‐ purinoceptors in the rat isolated mesenteric arterial bed

Cited by 69 publications

References 29 publications

Evidence for Multiple P2Y Receptors in Trabecular Meshwork Cells

Evidence for Multiple P2Y Receptors in Trabecular Meshwork Cells

The involvement of smooth muscle P2X receptors in the prolonged vasorelaxation response to purine nucleotides in the rat mesenteric arterial bed

Dinucleoside Polyphosphates

Contact Info

Product

Resources

About

Discrimination by PPADS between endothelial P_2Y‐ and P_2U‐ purinoceptors in the rat isolated mesenteric arterial bed