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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Harper, S. Charlton, S. J. Boarder, M. R. Webb, T. E. Ng, L. L. |
| Description | Author Affiliation: Harper S ( Department of Cell Physiology and Pharmacology, University of Leicester.) |
| Abstract | 1. Previous studies have shown that ATP and UTP are able to stimulate phospholipase C (PLC) and proliferation in cultured aortic smooth muscle cells. Here we set out to characterize the receptor responsible, and investigate a possible role for p42 and p44 mitogen activated protein kinase (MAPK) in the proliferative response. 2. The phospholipase C response of spontaneously hypertensive rat (SHR) derived aortic smooth muscle cells in culture showed that the response to ATP was partial compared to the response to UTP. 3. Further studies characterized the responses of the SHR derived cells. UTP was the only full agonist with the SHR cells; UDP gave a partial response while ADP, 2-methythio-ATP and alpha,beta-methylene ATP were essentially ineffective. The response to UDP was almost lost in the presence of hexokinase, consistent with this being due to extracellular conversion to UTP. These observations are inconsistent with the response being mediated by either P2Y1 or P2Y6 receptors. 4. When increasing concentrations of ATP were present with a maximally effective concentration of UTP, the size of the response diminished, consistent with UTP and ATP acting at a single population of receptors for which ATP was a partial agonist. This is inconsistent with a response mainly at P2Y2 receptors. 5. 1321N1 cells transfected with human P2Y4 receptors gave a similar agonist response profile, with ATP being partial compared to UTP, loss of response to UDP with hexokinase treatment, and with the response to UTP diminishing in the presence of increasing concentrations of ATP. 6. Use of the reverse transcriptase-polymerase chain reaction confirmed the presence of mRNA encoding P2Y4 receptors in SHR derived vascular smooth muscle cells. Transcripts for P2Y2, P2Y4 and P2Y6 receptors, but not P2Y1 receptors, were detected. 7. Stimulation of SHR derived cells with UTP enhanced the tyrosine phosphorylation of both p42 and p44 MAPK, and the incorporation of [3H]-thymidine into DNA. Both these responses were diminished in the presence of an inhibitor of activation of MAPK. 8 These results lead to the conclusion that in SHR derived cultured aortic smooth muscle cells, PLC responses to extracellular UTP and ATP are predominantly at P2Y4 receptors, and suggest that these receptors are coupled to mitogenesis via p42/p44 MAPK. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 124 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1998-06-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Adenosine Triphosphate Physiology Aorta, Thoracic Muscle, Smooth, Vascular Receptors, Purinergic P2 Uridine Triphosphate Agonists Amino Acid Sequence Animals Cytology Enzymology Metabolism Cells, Cultured Enzyme Activation In Vitro Techniques Molecular Sequence Data Polymerase Chain Reaction RNA, Messenger Biosynthesis Rats, Inbred SHR Rats, Inbred WKY Species Specificity Type C Phospholipases Comparative Study Research Support, Non-U.S. Gov't Pharmacology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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