Physiological properties of ATP-activated cation channels in rat brain microvascular endothelial cells

Abstract

Endothelial cells mediate the actions of a variety of vasoactive substances, including ATP. ATP vasodilatatory actions have been shown to depend on a calcium-dependent release of endothelium-derived relaxing factor(s) (EDRF). ATP induced a vasodilatation of pial penetrating microvessels when applied intraluminally; these relaxations were mediated by the endothelium and followed release of nitric oxide (NO), since they were sensitive to blockade of NO-synthesizing enzymes by NG-nitro-L-arginine (1 mM) and NG-mono-methyl-L-arginine (0.1 mM). We have also investigated the electrophysiological actions of extracellular ATP on rat brain microvascular (RBMEC) and bovine aortic endothelial cells (BAEC) using the patch-clamp technique. While BAEC were hyperpolarized by ATP (10 microM), ATP caused the activation of a depolarizing nonselective cation current in brain endothelial cells. NO production measurements by [3H]citrulline assay and by direct amperometric determination also revealed that after exposure to 1-100 microM ATP, RBMEC released NO. NO release from RBMEC was abolished by removal of external calcium. We conclude that, in the brain, ATP exerts its vasoactive roles by altering the electrophysiological properties of endothelial cells by acting on receptor-operated ion channels, thus providing a mechanism for calcium entry and subsequent release of EDRF.

P1,P4‐diadenosine 5′ tetraphosphate induces nitric oxide release from bovine aortic endothelial cells

“…The biological effects of adenine mononucleotides, but not the adenine dinucleotides, on endothelial cells have been well characterized. The major effect of adenine nucleotides on the endothelium is the stimulation of the synthesis and release of prostacyclin and NO [28–35]. Work presented in this communication demonstrates for the first time that Ap 4 A and Ap 2 A induce the release of NO from endothelial cells.…”

Analysis of purine- and pyrimidine-induced vascular responses in the isolated rat cerebral arteriole

“…These results suggest that 1) the receptor subtype mediating the dilation induced by UTP is different from that mediating the constriction induced by UTP and similar to that mediating the dilation induced by ATP and 2) UTP and ATP probably mediate dilations via endothelial P 2Y2 -receptor stimulation in the rat penetrating arteriole. In the cerebral circulation, release of nitric oxide and endothelium-derived hyperpolarizing factor, rather than prostacyclin, appears to be involved in the dilation to endothelial P 2Y1 -and P 2Y2receptor stimulation (25,26,38,60,61). In rat cerebral artery, endothelial P 2Y1 stimulation causes exclusively nitric oxide release, while P 2Y2 stimulation released nitric oxide and another not yet defined relaxation factor (60).…”

In Vitro Assessment of Tobacco Smoke Toxicity at the BBB: Do Antioxidant Supplements Have a Protective Role?

“…The NO measuring probe is inserted into the lumen downstream from the hollow fiber apparatus and another probe in the ECS compartment. NO is detected as previously described [96,97]. The on-line changes in NO were continuously measured using a PC-driven system.…”