This article is a commentary on Tölle et al., pp. 530–540 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2010.00914.x
Control of vascular tone by purines and pyrimidines
Version of Record online: 22 JUN 2010
© 2010 The Author. British Journal of Pharmacology © 2010 The British Pharmacological Society
British Journal of Pharmacology
Volume 161, Issue 3, pages 527–529, October 2010
How to Cite
Burnstock, G. (2010), Control of vascular tone by purines and pyrimidines. British Journal of Pharmacology, 161: 527–529. doi: 10.1111/j.1476-5381.2010.00937.x
- Issue online: 3 SEP 2010
- Version of Record online: 22 JUN 2010
- Received19 April 2010Accepted20 April 2010
- sympathetic nerves;
- endothelial cells;
In this Commentary, the roles of uridine adenosine tetraphosphate as an endothelium-derived contracting or relaxing factor described in the paper by Tölle et al. are considered and put into the wider context of the mechanisms of control of vascular tone by purinergic signalling via receptors located on both smooth muscle and endothelial cells.
uridine adenosine tetraphosphate
For many years control of vascular tone was understood to be via antagonistic sympathetic adrenergic vasoconstrictor and parasympathetic cholinergic vasodilator nerves. Then the seminal discovery by Furchgott of control of vascular tone via endothelium-derived relaxing factors opened up a whole new field. Endothelium-derived contracting factors were also identified.
Dual control of vascular tone by ATP was recognized (Burnstock and Kennedy, 1986). ATP released as a cotransmitter with noradrenaline from sympathetic nerves to produce contraction of vascular smooth muscle via P2X (ion channel) receptors; while ATP released from endothelial cells in response to changes in blood flow (shear stress) and hypoxia to act on P2Y (G protein-coupled) receptors on endothelial cells to release nitric oxide (NO) resulting in vasodilation (Burnstock, 1990). Subsequently, more purinoceptor subtypes were recognized on both vascular smooth muscle (P2X1 (in some vessels P2X2 and P2X4), P2Y1 and P2Y2) and endothelial cells (in various vessels P2X1, P2X2, P2X3, P2X4 and P2Y1, P2Y2, P2Y4 and P2Y11) in different vessels, mediated by pyrimidines as well as purines and diadenosine polyphosphates (see Burnstock, 2008). In 2005, uridine adenosine tetraphosphate (Up4A) and adenosine tetraphosphate were shown to be endothelial contracting factors probably acting via P2X1 receptors on smooth muscle (Jankowski et al., 2005; Tölle et al., 2008).
A paper by the same group in this issue of the BJP, extends this finding to show that in the rat isolated perfused kidney model, in addition to smooth muscle P2X1 receptor-mediated constrictor activation, Up4A showed dose-dependent P2Y2 receptor-mediated long-lasting vasoconstriction. Further, they demonstrated that vasoconstriction by Up4A was followed by vasodilation mediated by P2Y1 and P2Y2 receptor activation of endothelial cells leading to release of NO. Whether the actions of Up4A described in this paper are confined to vessels in the kidney or are more widely utilized in the vascular system needs to be resolved. Nevertheless, this work is important in emphasizing the complex and variable purinergic pathways involved in control of vascular tone in different vessels and its relevance to both the physiology and pathophysiology of the vascular system. Figure 1 illustrates the current knowledge of the involvement of purinergic receptor subtypes in these regulatory mechanisms and highlights the new information produced by the paper by Tölle et al. (2010).
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