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Characterisation of an ATP receptor mediating mitogenesis in vascular smooth muscle cells

Erlinge, David LU ; You, Junping; Wahlestedt, Claes and Edvinsson, Lars LU (1995) In European Journal of Pharmacology 289(1). p.135-149
Abstract
Adenosine triphosphate (ATP), a co-transmitter in sympathetic nerves and released from platelets, has recently been shown to stimulate growth of vascular smooth muscle cells. It might therefore contribute to the development of vascular hypertrophy seen in hypertension and atherosclerosis. We aimed at characterising the receptor mediating this mitogenic effect in rat aorta smooth muscle cells. The potency of agonists indicates a P2 purinoceptor since ATP > or = ADP >> AMP, adenosine. The P2x-receptor subtype, which is responsible for ATP induced vasoconstriction in rat aorta, does not mediate the mitogenic effect since alpha, beta-methyleneATP had no effect and beta, gamma-methyleneATP had lower potency than ATP. The P2Y-receptor... (More)
Adenosine triphosphate (ATP), a co-transmitter in sympathetic nerves and released from platelets, has recently been shown to stimulate growth of vascular smooth muscle cells. It might therefore contribute to the development of vascular hypertrophy seen in hypertension and atherosclerosis. We aimed at characterising the receptor mediating this mitogenic effect in rat aorta smooth muscle cells. The potency of agonists indicates a P2 purinoceptor since ATP > or = ADP >> AMP, adenosine. The P2x-receptor subtype, which is responsible for ATP induced vasoconstriction in rat aorta, does not mediate the mitogenic effect since alpha, beta-methyleneATP had no effect and beta, gamma-methyleneATP had lower potency than ATP. The P2Y-receptor subtype was excluded since the selective agonist 2-methylthioATP had weak effect with lower potency than ATP. When we studied the involvement of other nucleotides similar effects were seen of the purines ATP, GTP and ITP; also the pyrimidine UTP had powerful mitogenic effects (Emax = 52% of ATP) with similar potency. Nucleotides with fewer phosphate groups showed a stepwise fall in mitogenic effect. This indicates involvement of a nucleotide-receptor (P2U). Ap4A were of equal potency and effect as ATP. There was strong correlation between the mitogenic effects of the nucleotides and analogues with both 45Ca(2+)-influx and inositol phosphate (IP) production, indicating that they may participate in mediating the mitogenic response. This is the first study describing the potencies for the mitogenic effects of the selective ATP-analogues and other nucleotides in vascular smooth muscle cells. The receptor characterisation indicates a nucleotide-receptor similar to the receptor which stimulates 45Ca(2+)-influx and inositol phosphate-formation in rat aorta smooth muscle cells. Substances related to ATP such as GTP, ITP, UTP and Ap4A which also can be released extracellularly in vivo stimulate mitogenesis of rat aorta smooth muscle cells through the same receptor. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ATP, Mitosis, ATP receptor, Smooth muscle cell
in
European Journal of Pharmacology
volume
289
issue
1
pages
135 - 149
publisher
Elsevier
external identifiers
  • pmid:7781705
  • scopus:0028985704
ISSN
1879-0712
DOI
10.1016/0922-4106(95)90178-7
language
English
LU publication?
yes
id
5c4779fe-2ed4-410d-8e69-966a2d4d5f12 (old id 1109142)
date added to LUP
2008-07-25 14:16:31
date last changed
2017-11-12 03:32:13
@article{5c4779fe-2ed4-410d-8e69-966a2d4d5f12,
  abstract     = {Adenosine triphosphate (ATP), a co-transmitter in sympathetic nerves and released from platelets, has recently been shown to stimulate growth of vascular smooth muscle cells. It might therefore contribute to the development of vascular hypertrophy seen in hypertension and atherosclerosis. We aimed at characterising the receptor mediating this mitogenic effect in rat aorta smooth muscle cells. The potency of agonists indicates a P2 purinoceptor since ATP > or = ADP >> AMP, adenosine. The P2x-receptor subtype, which is responsible for ATP induced vasoconstriction in rat aorta, does not mediate the mitogenic effect since alpha, beta-methyleneATP had no effect and beta, gamma-methyleneATP had lower potency than ATP. The P2Y-receptor subtype was excluded since the selective agonist 2-methylthioATP had weak effect with lower potency than ATP. When we studied the involvement of other nucleotides similar effects were seen of the purines ATP, GTP and ITP; also the pyrimidine UTP had powerful mitogenic effects (Emax = 52% of ATP) with similar potency. Nucleotides with fewer phosphate groups showed a stepwise fall in mitogenic effect. This indicates involvement of a nucleotide-receptor (P2U). Ap4A were of equal potency and effect as ATP. There was strong correlation between the mitogenic effects of the nucleotides and analogues with both 45Ca(2+)-influx and inositol phosphate (IP) production, indicating that they may participate in mediating the mitogenic response. This is the first study describing the potencies for the mitogenic effects of the selective ATP-analogues and other nucleotides in vascular smooth muscle cells. The receptor characterisation indicates a nucleotide-receptor similar to the receptor which stimulates 45Ca(2+)-influx and inositol phosphate-formation in rat aorta smooth muscle cells. Substances related to ATP such as GTP, ITP, UTP and Ap4A which also can be released extracellularly in vivo stimulate mitogenesis of rat aorta smooth muscle cells through the same receptor.},
  author       = {Erlinge, David and You, Junping and Wahlestedt, Claes and Edvinsson, Lars},
  issn         = {1879-0712},
  keyword      = {ATP,Mitosis,ATP receptor,Smooth muscle cell},
  language     = {eng},
  number       = {1},
  pages        = {135--149},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Characterisation of an ATP receptor mediating mitogenesis in vascular smooth muscle cells},
  url          = {http://dx.doi.org/10.1016/0922-4106(95)90178-7},
  volume       = {289},
  year         = {1995},
}