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PMID: 8019751 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Differential regulation of inositol 1,4,5-trisphosphate by co-existing P2Y-purinoceptors and nucleotide receptors on bovine aortic endothelial cells.

British journal of pharmacology ·Vol. 111 ·No. 3 ·1994-03-00 ·Pages 723-8

Purkiss JR, Wilkinson GF, Boarder MR

Abstract

1. We have examined the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) responses in bovine aortic endothelial (BAE) cells to purines (ATP, ADP and analogues) and the pyrimidine, uridine triphosphate (UTP). 2. Exchange of medium on BAE cells in the absence of agonist was found to be a stimulus for Ins(1,4,5)P3 generation. BAE cells stimulated with 100 microM ATP, 30 microM 2MeSATP (an agonist at P2Y-purinoceptors but not nucleotide receptors) or 100 microM UTP (an agonist at nucleotide receptors but not P2Y-purinoceptors) gave Ins(1,4,5)P3 responses above that caused by exchange of medium. The time course was rapid, with peak response within the first 5 s and levels returning close to basal after 30 s of stimulation. 3. Significant differences in Ins(1,4,5)P3 responses to 100 microM UTP and 30 microM 2MeSATP stimulation were observed. The response to UTP was reproducibly more sustained than that to 2MeSATP. 4. Stimulation of BAE cells with 100 microM UTP plus 30 microM 2MeSATP produced a response statistically indistinguishable from that predicted by addition of the responses to the two agonists in isolation. 5. The Ins(1,4,5)P3 response to UTP was attenuated to 25% of control by pretreatment of BAE cells with pertussis toxin. Responses to 2MeSATP and ADP were essentially unaffected. ATP stimulation was reduced to 65% of control. 6. Activation of protein kinase C with tetradecanoyl phorbol acetate (TPA) profoundly inhibited Ins(1,4,5)P3 responses to 2MeSATP and ADP but had no effect on UTP stimulation. The protein kinase C inhibitor, Ro 31-8220, enhanced responses to 2MeSATP, ADP and ATP but no effect was observed on UTP stimulation. 7. These observations show that nucleotide and P2Y-receptors mobilise the second messenger Ins(1,4,5)P3 by separate routes resulting in different patterns of generation and suggest that while ATP activates both receptors, ADP principally influences these cells by interacting with the P2Y-purinoceptors.

MeSH Terms
Adenosine Triphosphate/analogs & derivatives,pharmacology Animals Aorta/drug effects,physiology,ultrastructure Cattle Cells, Cultured Endothelium, Vascular/drug effects,physiology,ultrastructure Enzyme Activation Indoles/pharmacology Inositol 1,4,5-Trisphosphate/metabolism,physiology Nucleotides/pharmacology Protein Kinase C/antagonists & inhibitors,metabolism Purines/pharmacology Receptors, Purinergic/physiology Second Messenger Systems/physiology Tetradecanoylphorbol Acetate/pharmacology Thionucleotides/pharmacology Time Factors Uridine Triphosphate/pharmacology
Chemicals
Indoles Nucleotides Purines Receptors, Purinergic Thionucleotides Inositol 1,4,5-Trisphosphate Adenosine Triphosphate Protein Kinase C Tetradecanoylphorbol Acetate Uridine Triphosphate Ro 31-8220 2-methylthio-ATP
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Purkiss J R
Department of Pharmacology & Therapeutics, University of Leicester.
Wilkinson G F
Boarder M R
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32 references, click to expand
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1111/j.1476-5381.1994.tb14797.x
Published
1994-03-00
Pages
723-8
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1910100
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1111/j.1476-5381.1994.tb14797.x PMC Full Text View journal details
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