ATP mediates coronary vasoconstriction via P2x-purinoceptors and coronary vasodilatation via P2y-purinoceptors in the isolated perfused rat heart

Hopwood, Alexandra M.; Burnstock, Geoffrey

doi:10.1016/0014-2999(87)90777-1

Cited by 91 publications

(82 citation statements)

References 12 publications

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“…Consistent with our results are reports that theophylline and CGS15943 signi®cantly attenuated ATP-mediated coronary vasodilation in isolated hearts (Bunger et al, 1975;Kroll & Schrader, 1993;Hopwood & Burnstock, 1987). In contrast are reports that AdoR antagonists caused no signi®cant attenuation of ATP-mediated coronary vasodilation (Brown et al, 1992;Vials & Burnstock, 1994;Giles & Wilcken, 1977).…”

Section: Discussionsupporting

confidence: 92%

“…The transient high concentration of ATP may cause activation of P 2 receptors that have both high and low a nities for ATP. Activation of these receptors may lead to either a faster onset of coronary vasodilation caused by ATP or an initial P 2X receptor-mediated coronary vasoconstriction that is followed by vasodilation (Godecke et al, 1996;Gordon, 1986;Hopwood & Burnstock, 1987;Olsson & Pearson, 1990). Thus it is possible that the bolus administration of high concentrations of ATP may allow the investigator to observe activation by ATP of P 2 receptors that cause transient changes in coronary conductance that were not seen in this study.…”

Section: Discussionmentioning

confidence: 80%

“…Studies on isolated vessels and isolated hearts support the view that ATP causes coronary vasodilation by P 2Y receptor activation (Brown et al, 1992;Corr & Burnstock. 1991;Fleetwood & Gordon, 1987;Gordon, 1986;Hopwood & Burnstock, 1987;Matsumoto et al, 1997;Olsson & Pearson, 1990;Simonsen et al, 1997;Vials & Burnstock, 1994;Godecke et al, 1996). However, antagonism of ATP-induced coronary vasodilation by AdoR antagonists implicates activation of A 2A -AdoRs in the action of ATP (White & Angus, 1987;Bunger et al, 1975;King et al, 1990;Kroll & Schrader, 1993).…”

Section: Introductionmentioning

confidence: 99%

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Role of A_2A‐adenosine receptor activation for ATP‐mediated coronary vasodilation in guinea‐pig isolated heart

Erga

Seubert

Liang

et al. 2000

British J Pharmacology

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1 Adenosine-5'-triphosphate (ATP) and adenosine are potent coronary vasodilators. ATP is rapidly converted to adenosine by ectonucleotidases. We examined whether coronary vasodilation caused by exogenous ATP is mediated by P 2 receptor activation or by A 2A -adenosine receptor activation. 2 E ects of interventions on coronary conductance were determined by measuring coronary perfusion pressure in guinea-pig isolated hearts perfused at a constant¯ow of 10 ml min 71 . 3 ATP and adenosine both caused sustained, concentration-dependent increases of coronary conductance. Maximal responses to both agonists were equivalent. The values of pD 2 (+s.e.mean) for ATP and adenosine were 6.68+0.04 and 7.06+0.05, respectively. Adenosine was signi®cantly more potent than ATP (P50.0001, n=10).4 The values of pIC 50 for the selective A 2A -adenosine receptor antagonist SCH58261 to antagonize equivalent responses to ATP and adenosine were 8.28+0.08 and 8.28+0.06 (P=0.99, n=6), respectively. 5 The non-selective adenosine receptor antagonists xanthine amine congener (XAC) and CGS15943 antagonized similarly the equivalent vasodilations caused by ATP (pIC 50 values 7.48+0.04 and 7.45+0.06, respectively) and adenosine (pIC 50 values 7.37+0.13 and 7.56+0.11). 6 In contrast to ATP and adenosine, the two P 2 agonists 2-methylthio-ATP and uridine-5'-triphosphate failed to cause stable increases of coronary conductance, caused desensitization of vasodilator responses, and were not antagonized by SCH 58261, 8-parasulphophenyltheophylline, or XAC. 7 Glibenclamide attenuated coronary vasodilations caused by ATP and adenosine by 88 and 89%, respectively, but failed to attenuate those caused by 2-methylthio-ATP.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

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Role of A_2A‐adenosine receptor activation for ATP‐mediated coronary vasodilation in guinea‐pig isolated heart

Erga

Seubert

Liang

et al. 2000

British J Pharmacology

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“…There is compelling evidence that ATP acts as a neurotransmitter in vascular smooth muscle and is coreleased with norepinephrine from sympathetic nerves (9,18,21,29). Burnstock and Kennedy (11) proposed the subdivision of P2 purinergic receptors into P2X, which mediate vasoconstriction, and P2Y, which mediate vasodilation.…”

Section: Discussionmentioning

confidence: 99%

“…blood flow; sympatholysis; autonomic nervous system; dogs FOR YEARS, SYMPATHETIC VASOCONSTRICTION has been thought to be mediated entirely by norepinephrine released from sympathetic nerve terminals. However, there is strong evidence that ATP acts as a neurotransmitter in vascular smooth muscle and is coreleased with norepinephrine from sympathetic nerves (9,18,21,29). The release of ATP is thought to stimulate a purinergic receptor (P2).…”

mentioning

confidence: 99%

Vasoconstriction in active skeletal muscles: a potential role for P2X purinergic receptors?

Buckwalter

Hamann

Clifford

2003

Journal of Applied Physiology

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Vasoconstriction in active skeletal muscles: a potential role for P2X purinergic receptors? J Appl Physiol 95: 953-959, 2003. First published May 23, 2003 10.1152/ japplphysiol.00173.2003.-There is evidence that ATP acts as a neurotransmitter in vascular smooth muscle and is coreleased with norepinephrine from sympathetic nerves. We hypothesized that P2X-receptor stimulation with the selective P2X-receptor agonist ␣,␤-methylene ATP would produce vasoconstriction in resting and exercising skeletal muscle. Six mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. The selective P2X agonist ␣,␤-methylene ATP was infused as a bolus into the femoral artery catheter at rest and during mild, moderate, and heavy exercise. Intra-arterial infusions of ␣,␤-methylene ATP elicited reductions in vascular conductance of 54 Ϯ 5, 49 Ϯ 8, 39 Ϯ 8, and 30 Ϯ 6% at rest, 3 miles/h, 6 miles/h, and 6 miles/h at a 10% grade, respectively. The agonist infusions did not affect blood flow in the contralateral iliac artery. To examine whether nitric oxide is responsible for the attenuated vasoconstrictor response to P2X stimulation, the infusions were repeated in the presence of N G -nitro-L-arginine methyl ester. After nitric oxide synthase blockade, intraarterial infusions of ␣,␤-methylene ATP elicited reductions in vascular conductance of 56 Ϯ 7, 61 Ϯ 8, 52 Ϯ 9, and 40 Ϯ 7% at rest, 3 miles/h, 6 miles/h, and 6 miles/h at a 10% grade, respectively. P2X-receptor responsiveness was attenuated during exercise compared with rest. Blockade of nitric oxide production did not affect the attenuation of P2X-receptor responsiveness during exercise. These data support the hypothesis that P2X purinergic receptors can produce vasoconstriction in exercising skeletal muscle. blood flow; sympatholysis; autonomic nervous system; dogs FOR YEARS, SYMPATHETIC VASOCONSTRICTION has been thought to be mediated entirely by norepinephrine released from sympathetic nerve terminals. However, there is strong evidence that ATP acts as a neurotransmitter in vascular smooth muscle and is coreleased with norepinephrine from sympathetic nerves (9,18,21,29). The release of ATP is thought to stimulate a purinergic receptor (P2). P2X purinergic receptors, which mediate vasoconstriction, are found predominantly in vascular smooth muscle, whereas P2Y purinergic receptors, which mediate vasodilation, are primarily located on endothelial cells (11). P2X receptors on vascular smooth muscle cells are preferentially stimulated by ATP from sympathetic nerve endings (17). Although two recent studies (1,19) showed that P2X-receptor stimulation produces vasoconstriction in the hindlimb of anesthetized cats and rats, it is unknown whether stimulation of P2X receptors in the arterial vasculature of skeletal muscle will produce vasoconstriction during exercise.In the past, the ability of the sympathetic nervous system to restrain blood flow in active skeletal muscle has been questioned (14,24,26)...

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ATP‐loaded liposomes for treatment of myocardial ischemia

Hartner

Verma

Levchenko

et al. 2009

WIREs Nanomed Nanobiotechnol

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A major obstacle to drug therapy for treatment of potential myocardial infarction is the limited access to the ischemic myocardium by drugs in an active form. Encouraging results have been reported with liposomes loaded with ATP in a variety of in vitro and in vivo models. We describe methods for optimized encapsulation of ATP in liposomes, enhancement of their effectiveness by increasing circulation time, and targeting of injured myocardial cells with surface attached antimyosin. In isolated ischemic rat hearts, ATP-loaded liposomes and ATP-loaded immunoliposomes effectively protected myocardium from ischemia/reperfusion damage as measured by systolic and diastolic functional improvements. In vivo, in rabbits with induced localized myocardial ischemia, liposomal encapsulation of ATP significantly diminished the proportion of ventricular muscle at risk that was irreversibly damaged during reperfusion. Therefore, ATP encapsulated in liposomes can provide an effective exogenous source for in vivo application which can protect ischemically damaged hearts.

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ATP mediates coronary vasoconstriction via P2x-purinoceptors and coronary vasodilatation via P2y-purinoceptors in the isolated perfused rat heart

Cited by 91 publications

References 12 publications

Role of A_2A‐adenosine receptor activation for ATP‐mediated coronary vasodilation in guinea‐pig isolated heart

Role of A_2A‐adenosine receptor activation for ATP‐mediated coronary vasodilation in guinea‐pig isolated heart

Vasoconstriction in active skeletal muscles: a potential role for P2X purinergic receptors?

ATP‐loaded liposomes for treatment of myocardial ischemia

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ATP mediates coronary vasoconstriction via P2x-purinoceptors and coronary vasodilatation via P2y-purinoceptors in the isolated perfused rat heart

Cited by 91 publications

References 12 publications

Role of A2A‐adenosine receptor activation for ATP‐mediated coronary vasodilation in guinea‐pig isolated heart

Role of A2A‐adenosine receptor activation for ATP‐mediated coronary vasodilation in guinea‐pig isolated heart

Vasoconstriction in active skeletal muscles: a potential role for P2X purinergic receptors?

ATP‐loaded liposomes for treatment of myocardial ischemia

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Product

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Role of A_2A‐adenosine receptor activation for ATP‐mediated coronary vasodilation in guinea‐pig isolated heart

Role of A_2A‐adenosine receptor activation for ATP‐mediated coronary vasodilation in guinea‐pig isolated heart