Stimulation of vascular prostacyclin synthesis by extracellular ADP and ATP

Boeynaems, Jean‐Marie; Galand, Nicole

doi:10.1016/0006-291x(83)91829-6

Cited by 78 publications

(38 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While this study has not revealed the mechanism of action for the response to a, 13-MeATP, it has revealed that stimulation of the P2 -purinoceptor results in the formation of a prostanoid, since ATP and 2MeSATP were inhibited by indomethacin. This is consistent with a number of mammalian vascular systems (Needleman et al, 1974;Boeynaems & Galand, 1983) where prostaglandin synthesis is initiated by ATP at the endothelial level, mediating vasodilatation (see Moncada, 1982). However, in this preparation, the prostaglandin is not endothelial in origin, since vasoconstriction to 2MeSATP occurred even when the endothelium was not intact (as revealed by the lack of vasodilatation to ACh).…”

Section: Discussionsupporting

confidence: 87%

Responses of the aorta of the garter snake (Thamnophis sirtalis parietalis) to purines

Knight

Burnstock

1995

British J Pharmacology

View full text Add to dashboard Cite

1 Isolated aortic rings from the garter snake (Thamnophis sirtalis parietalis) were investigated in order to identify and classify responses to adenosine and adenosine 5'-triphosphate (ATP) and their analogues as part of a comparative study of vertebrate purinoceptors. 2 Adenosine, D-5'-(N-ethylcarboxamide) adenosine (NECA), R-and S-N6-(2-phenylisopropyl) adenosine (R-and S-PIA) and 2-chloroadenosine (2-CA) all concentration-dependently relaxed aorta preconstricted with noradrenaline (NA). The order of potency was: NECA > R-PIA = 2-CA> adenosine> S-PIA. Individual pD2 values for the analogues were: NECA 7.12 ± 0.13 (9), R-PIA 5.93 ± 0.25 (7), 2-CA 5.64 ± 0.40 (5), adenosine 5.04 ± 0.10 (13) and S-PIA 4.26 ± 0.10 (7). The order of potency has characteristics of both Al and A2 receptors and cannot satisfactorily be classified according to the P,-(adenosine) purinoceptor subtypes established in mammalian preparations.3 ATP, x,p-methylene ATP (aj-MeATP), 2-methylthio ATP (2MeSATP), P,Y-methylene ATP (P,T,-MeATP) and uridine 5'-triphosphate (UTP) all concentration-dependently constricted the isolated aorta.The order of potency was aj-MeATP = 2MeSATP > ATP >,,y-MeATP > UTP. Only ATP, ,-MeATP and 2MeSATP consistently produced a maximum response; pD2 values were: ATP 3.98 ± 0.07 (10), aP-MeATP 5.86 ± 0.15 (12) and 2MeSATP 6.06 ± 0.23 (9). In vessels preconstricted with NA neither ATP nor 2MeSATP caused relaxation in the presence or absence of the endothelium.4 Suramin (0.1 mM) inhibited vasoconstriction to ATP, a,P-MeATP, 2MeSATP and P,y-MeATP; however, since contractions to ATP and analogues did not reach a maximum response in the presence of this and other antagonists, pD2 values could not be calculated.5 Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 30 jiM), a P2x-purinoceptor antagonist, antagonized constrictions to aP-MeATP only. Reactive blue 2 (RB2; 30 gM), a P2Y-purinoceptor antagonist, inhibited vasoconstrictions to 2MeSATP only.6 Indomethacin (30 pM) inhibited vasoconstriction in response to ATP and 2MeSATP, but not a,,-MeATP, suggesting that the presence of an unaltered phosphate chain on the ATP analogue was necessary to stimulate the production of a prostanoid.7 Repeated administration of E,4-MeATP (3 jiM) caused desensitization of the receptor responsible for the constriction due to axj-MeATP whereas the responses to ATP and 2MeSATP were unaltered. 8 In summary, both P,-purinoceptors mediating vasodilatation and P2-purinoceptors mediating vasoconstriction are present on the garter snake aorta. However, in contrast to mammalian vessels, both P2x and P2Y subtypes mediate vasoconstriction. There was no evidence for vasodilatation to ATP or analogues. Stimulation of the P2-purinoceptor by ATP and 2MeSATP caused the synthesis of a prostanoid. In addition, the possibility of a receptor activated by ATP, separate from P2X and P2Y subtypes is discussed since contractions to ATP proved to be insensitive to both PPADS and RB2. A comparison is made of purinoceptors in the garter snake aorta with those...

show abstract

Section: Discussionsupporting

confidence: 87%

Responses of the aorta of the garter snake (Thamnophis sirtalis parietalis) to purines

Knight

Burnstock

1995

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Adenosine could dilate the arteries through release of prostanoids, as has been found for some vasodilators (Boeynaems & Galand, 1983;Forstermann et al, 1986;Gryglewski et al, 1986). However, indomethacin did not affect adenosineinduced dilatation, indicating that metabolites of the arachidonic acid cascade such as prostacyclin are unlikely to be candidates for mediating the action of adenosine.…”

Section: Discussionmentioning

confidence: 78%

Evidence for the involvement of cyclic GMP in adenosine‐induced, age‐dependent vasodilatation

Moritoki¹,

Matsugi²,

Takase³

et al. 1990

British J Pharmacology

View full text Add to dashboard Cite

1 Adenosine-induced dilatation of rat aorta was present in aorta taken from 4 week-old rats, attenuated with increase in age of rats to 8 weeks, and was virtually absent in the aorta from 12 week-old rats. 2 Removal of the endothelium by mechanical rubbing attenuated adenosine-induced dilatation. 3 Haemoglobin and methylene blue partly reversed the adenosine-induced endothelium-dependent dilatation. 4 The order of potency of adenosine derivatives was 5'-(N-ethylcarboxamido)indicating that adenosine receptors mediating the dilatation are of the A2 subtype. 5 [3H]-NECA bound to preparations of membranes from rats of 4 weeks old; it was displaced more effectively by NECA and the A2 ligand CV-1808 than by the A1 ligands CHA and S-PIA. ligands CHA and S-PIA. 6 The number but not affinity of specific binding sites for NECA decreased considerably with increase in age of rats to 8 weeks, and binding sites for [3H]-NECA were hardly detected in membrane preparations from rats of 20 weeks old. 7 Adenosine caused a marked increase in cyclic GMP production, but did not induce an increase in the cyclic AMP level. 8 This increase in cyclic GMP production induced by adenosine was abolished by methylene blue or 8-phenyltheophylline, or by removal of the endothelium. 9 The age-associated decrease in adenosine-induced dilatation was found to be associated with a reduction in the formation of cyclic GMP, but not of cyclic AMP. 10 These results suggest that adenosine causes dilatation via A2 receptors by inducing production of an endothelium-derived relaxing factor (EDRF), which in turn stimulates soluble guanylate cyclase, and so increases production of cyclic GMP. It is also suggested that the main reason for the age-associated decrease in adenosine-induced dilatation is a decrease in the number of A2-receptors or the ability of the endothelium to produce EDRF, leading to decreased production of cyclic GMP.

show abstract

“…Although several prior studies have also shown that ATP induces prostacyclin synthesis by the endothelium, those studies were performed on cultured cells or perfused arterial segments. [17][18][19] Stimulation of cells with ATP induces an increase in [Ca 2ϩ ] i by both activation of Ca 2ϩ release from intracellular Ca 2ϩ stores and Ca 2ϩ influx through ion channels in the plasma membrane. 20,21 Removal of extracellular Ca 2ϩ pre- vents the Ca 2ϩ influx that is essential for maintaining a sustained increase in [Ca 2ϩ ] i ; such removal was found to abolish ATP-induced prostacyclin synthesis in these vessels.…”

Section: Discussionmentioning

confidence: 99%

Calcium-Dependent Synthesis of Prostacyclin in ATP-Stimulated Venous Endothelial Cells

2002

View full text Add to dashboard Cite

Abstract-Prostacyclin is a powerful vasodilator that is released from vascular endothelial cells. Previous studies in our laboratory have indicated that arachidonic acid metabolites from venous endothelium play an important role in the dilation of adjacent arterioles during muscle stimulation. Furthermore, recent studies have suggested that ATP released from red blood cells during hypoxia stimulates dilation of arterioles. We tested the hypothesis that an ATP-induced increase in intracellular Ca 2ϩ in venous endothelium promotes prostacyclin synthesis. Small branches of femoral veins were isolated from male golden hamsters, placed in a 1 mL bath, and cannulated for perfusion with 3-(N-morpholino) propanesulfonic acid (MOPS)-buffered physiological salt solution at 37°C. Prostacyclin synthesis was determined by enzyme immunoassay of bath solution. Perfusion of veins with ATP increased prostacyclin synthesis from 50Ϯ5 to 627Ϯ46 pg/mL (nϭ49). ATP-induced prostacyclin synthesis was inhibited by removal of extracellular Ca 2ϩ , chelation of intracellular Ca 2ϩ with 1,2-bis(2-aminophenoxy)ethane-N,N,NЈ,NЈ-tetraacetic acid (BAPTA) (10 mol/L for 10 minutes), and preincubation with cytosolic phospholipase A 2 (PLA 2 ) inhibitors, AACOCF 3 , and bromoenol lactone. Changes in intracellular Ca 2ϩ in cultured human venous endothelial cells were assessed by fura-2 spectrofluorometry. ATP induced a transient Ca 2ϩ peak within seconds, and the subsequent Ca 2ϩ plateau was abolished by removal of extracellular Ca2ϩ . An increase in prostacyclin synthesis was detected in these cells 2 minutes after application of ATP. These findings suggest that the ATP-induced increase in intracellular Ca 2ϩ stimulates prostacyclin synthesis in venous endothelial cells. Vasodilators released from the endothelium include the arachidonic acid metabolite prostacyclin, nitric oxide, and endothelium-derived hyperpolarizing factor. However, the quantitative role of these vasodilators in different regions of the vasculature has not been characterized. Nitric oxide appears to have a minimal role in regulating arteriolar diameter during an increase in metabolic rate. [3][4][5] Previous studies from our laboratory have shown that arachidonic acid metabolites make a major contribution to the regulation of arteriolar diameter during muscle stimulation. 6,7 Arachidonic acid is released from membrane phospholipids through the direct action of phospholipase A 2 (PLA 2 ). Further metabolism of arachidonic acid generates three main groups of eicosanoids: prostaglandins and thromboxanes by cyclooxygenase; leukotrienes and lipoxins by lipoxygenase; and epoxides by cytochrome P-450 epoxygenase. Prostacyclin (prostaglandin I 2 ) is a very powerful vasodilator that is produced primarily in vascular endothelial cells. 8 There are both secretory and intracellular forms of PLA 2 . 9 The cytosolic form of PLA 2 includes both Ca 2ϩ -dependent and Ca 2ϩ -independent isozymes. However, it is not yet certain which of these enzymes is responsible for the release of arachidonic...

show abstract

Stimulation of vascular prostacyclin synthesis by extracellular ADP and ATP

Cited by 78 publications

References 8 publications

Responses of the aorta of the garter snake (Thamnophis sirtalis parietalis) to purines

Responses of the aorta of the garter snake (Thamnophis sirtalis parietalis) to purines

Evidence for the involvement of cyclic GMP in adenosine‐induced, age‐dependent vasodilatation

Calcium-Dependent Synthesis of Prostacyclin in ATP-Stimulated Venous Endothelial Cells

Contact Info

Product

Resources

About