Purinoceptor mediated stimulation of prostacyclin release in the porcine pulmonary vasculature

Hellewell, Paul G.; Pearson, Jeremy D.

doi:10.1111/j.1476-5381.1984.tb16507.x

Cited by 28 publications

(8 citation statements)

References 35 publications

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“…Additionally, because ATP induces the production of prostaglandin (including prostacyclin) by various vascular beds and by cultured endothelial cells (Minkes et al, 1973;Boeynaems & Galand, 1983;Pearson et al, 1983;Hellewell & Pearson, 1984) we examined whether stimulation of prostaglandin production was involved in mediating the effects of nucleotides on rat coronary vessels.…”

Section: Introductionmentioning

confidence: 99%

Purinoceptors in the rat heart

Fleetwood

Gordon

1987

British J Pharmacology

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1 The effects of an intracoronary bolus of adenosine triphosphate (ATP), a,p-methylene ATP (APCPP), ,y-methylene ATP (APPCP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and adenosine on coronary tone and ventricular myocardial contraction were investigated in the perfused rat heart. 2 Adenine nucleotides, given by bolus injection were negatively inotropic in amounts > 3 x 10-7 mol. The potency order was ATP>ADP> AMP. Adenosine (<1 x 10-5mol) had no effect on ventricular myocardial contraction. 3 Adenine nucleotides and adenosine (1 x 10-'-1 x 10-' mol) reduced coronary tone. The potency order was ATP > ADP > AMP = adenosine. The ATP analogue APPCP was less active than ATP at reducing coronary tone, and APCPP had no vasodilator effect. This suggests the presence of a P2-purinoceptor, subclass P2w which mediates vasodilatation. 4 ATP and ADP increased the concentration of prostacyclin (measured as 6-keto prostaglandin Fa) in the perfusate, but only after injection of > 3 x 10-7 mol, suggesting that the vasodilator responses to ATP and ADP were not mediated by prostacyclin. AMP and adenosine had no effect, even at x 105mol. 5 At a dose of 3 x 10-mol, approximately 40% of ATP and 70% of ADP was converted to AMP and adenosine whilst passing through the heart. The amounts of AMP and adenosine formed, however, were insufficient to account for the vasodilator effects of ATP and ADP. 6 Vasodilatation mediated by AMP and adenosine was inhibited by an infusion of 8-phenyltheophylline (8-PT; 2 x 10-5 M) indicating interaction with a P1-purinoceptor. Vasodilatation induced by ATP (at doses at which AMP and adenosine had no action) was also depressed by 8-PT indicating either an action of ATP on PI-purinoceptors, or an effect of 8-PT on P2y receptors. 7 Vasodilatation induced by AMP was unaltered during an infusion of a,-methylene ADP (2 x 10-6 M, which inhibited breakdown of AMP to adenosine by 54.2 ± 1.5%, n = 4). This suggests that AMP acted directly, and it did not require conversion to adenosine to induce vasodilatation.

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Section: Introductionmentioning

confidence: 99%

Purinoceptors in the rat heart

Fleetwood

Gordon

1987

British J Pharmacology

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“…Porcine pulmonary vessels express P2 receptors that mediate the synthesis and release of prostacyclin (Hellewell and Pearson, 1984). In the isolated, blood-PURINERGIC SIGNALING IN THE AIRWAYS perfused, and ventilated rat lung, P2X receptors activated by ␣,␤-meATP caused vasoconstriction, whereas P2Y receptors, probably located largely on the endothelium, mediated a small vasodilator response (Liu et al, 1989;McCormack et al, 1989a).…”

Section: E Vasculaturementioning

confidence: 99%

Purinergic Signaling in the Airways

Burnstock

Brouns²,

Adriaensen³

et al. 2012

Pharmacol Rev

173

158

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“…Infusion of ATP at a concentration of 300 M resulted in a reduction in total pulmonary vascular resistance (Table 1), and this effect was confined to the upstream (arterial) vascular segment. ATP has been reported to produce vasodilation via stimulation of the endothelium to produce NO (5,8,11,12,16), arachidonic acid metabolites (13,23), and possible other endothelium-derived relaxing factors (36). The majority of the effect of ATP to reduce vascular resistance was inhibited by L-NAME suggesting that, under these experimental conditions, ATP acts largely, but not entirely, through stimulation of NO synthesis (Fig.…”

Section: Discussionmentioning

confidence: 89%

Extracellular ATP signaling in the rabbit lung: erythrocytes as determinants of vascular resistance

Sprague¹,

Olearczyk²,

Spence³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

106

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Previously, it was reported that red blood cells (RBCs) are required to demonstrate participation of nitric oxide (NO) in the regulation of rabbit pulmonary vascular resistance (PVR). RBCs do not synthesize NO; hence, we postulated that ATP, present in millimolar amounts in RBCs, was the mediator, which evoked NO synthesis in the vascular endothelium. First, we found that deformation of RBCs, as occurs on passage across the pulmonary circulation with increasing flow rate, evoked increments in ATP release. Here, ATP (300 nM), administered to isolated, salt solution-perfused (PSS) rabbit lungs, decreased total and upstream (arterial) PVR, a response inhibited by N G -nitro-L-arginine methyl ester (L-NAME, 100 M). In lungs perfused with PSS containing RBCs, L-NAME increased total and upstream PVR. In lungs perfused with PSS containing glibenclamide-treated RBCs, which inhibits ATP release, L-NAME was without effect. Apyrase grade VII (8 U/ml), which degrades ATP to AMP, was without effect on PVR in PSS-perfused lungs. These results are consistent with the hypothesis that ATP, released from RBCs as they traverse the pulmonary circulation, evokes endogenous NO synthesis.adenosine-5Ј triphosphate; red blood cell EXTRACELLULAR ATP has been suggested to play an important role in the regulation of vascular resistance in a number of vascular beds, including the kidney (24, 26), mesentery (5, 28), heart (17, 20), and lung (8,10,11,12,16,31). The spacial relationship between the cell that is the source of extracellular ATP and vascular smooth muscle is an important determinant of the vascular response to ATP. Thus ATP released from nerve terminals adjacent to vascular smooth muscle would be expected to activate purinergic receptors that produce contraction of that muscle (18,21). In contrast, ATP released from formed elements in the circulation such as red blood cells (RBCs) (6,9,31,33) or ATP released from the endothelium itself (27) would interact with purinergic receptors present on the endothelium. The stimulation of such receptors has been shown to result in the synthesis of endothelium-derived relaxing factors, including nitric oxide (NO) (5,8,12,11,16). Thus extracellular ATP released from nerve terminals would be expected to increase vascular resistance, whereas ATP released into the vascular lumen could be an important mechanism for decreasing vascular resistance.We reported previously that 1) ATP is released from rabbit RBCs as they traverse the pulmonary circulation (29) and 2) RBCs that are capable of releasing ATP were a requisite component in the perfusate of isolated rabbit lungs to demonstrate the participation of NO as a determinant of vascular resistance (31, 33). In the work presented here, we present evidence that ATP, in the absence of RBCs, is capable of promoting NO synthesis in the pulmonary circulation of the rabbit. Thus we determined the effect of ATP infused into the circulation of isolated rabbit lungs on vascular resistance. Moreover, we present evidence that the major mechanism by which ATP ac...

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Purinoceptor mediated stimulation of prostacyclin release in the porcine pulmonary vasculature

Cited by 28 publications

References 35 publications

Purinoceptors in the rat heart

Purinoceptors in the rat heart

Purinergic Signaling in the Airways

Extracellular ATP signaling in the rabbit lung: erythrocytes as determinants of vascular resistance

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