Differential Regulation of Inositol 1,4,5-trisphosphate by Co-existing P2Y-purinoceptors and Nucleotide Receptors on Bovine Aortic Endothelial Cells

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1994 Mar 1

PMID 8019751

Citations 13

Authors

J R Purkiss

G F Wilkinson

M R Boarder

Affiliations

Soon will be listed here.

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.

Citing Articles

Evidence for Purinergic Receptors in Vestibular Dark Cell and Strial Marginal Cell Epithelia of Gerbil.

Liu J, Kozakura K, Marcus D Audit Neurosci. 2012; 1(4):331-340.

PMID: 22582019 PMC: 3348583.

Capacitative Ca(2+) entry in vascular endothelial cells is mediated via pathways sensitive to 2 aminoethoxydiphenyl borate and xestospongin C.

Bishara N, Murphy T, Hill M Br J Pharmacol. 2002; 135(1):119-28.

PMID: 11786487 PMC: 1573124. DOI: 10.1038/sj.bjp.0704465.

Differential regulation of P2Y(11) receptor-mediated signalling to phospholipase C and adenylyl cyclase by protein kinase C in HL-60 promyelocytes.

Suh B, Kim T, Lee I, Kim K Br J Pharmacol. 2000; 131(3):489-97.

PMID: 11015299 PMC: 1572341. DOI: 10.1038/sj.bjp.0703581.

Vasoconstriction of intrapulmonary arteries to P2-receptor nucleotides in normal and pulmonary hypertensive newborn piglets.

McMillan M, Burnstock G, Haworth S Br J Pharmacol. 1999; 128(3):549-55.

PMID: 10516631 PMC: 1571657. DOI: 10.1038/sj.bjp.0702814.

Vasodilatation of intrapulmonary arteries to P2-receptor nucleotides in normal and pulmonary hypertensive newborn piglets.

McMillan M, Burnstock G, Haworth S Br J Pharmacol. 1999; 128(3):543-8.

PMID: 10516630 PMC: 1571658. DOI: 10.1038/sj.bjp.0702815.

References

Purkiss J, Wilkinson G, Boarder M . Evidence for a nucleotide receptor on adrenal medullary endothelial cells linked to phospholipase C and phospholipase D. Br J Pharmacol. 1993; 108(4):1031-7. PMC: 1908149. DOI: 10.1111/j.1476-5381.1993.tb13501.x. View

Wilkinson G, Purkiss J, Boarder M . The regulation of aortic endothelial cells by purines and pyrimidines involves co-existing P2y-purinoceptors and nucleotide receptors linked to phospholipase C. Br J Pharmacol. 1993; 108(3):689-93. PMC: 1908023. DOI: 10.1111/j.1476-5381.1993.tb12862.x. View

Booyse F, Sedlak B, RAFELSON Jr M . Culture of arterial endothelial cells: characterization and growth of bovine aortic cells. Thromb Diath Haemorrh. 1975; 34(3):825-39. View

Martin W, Cusack N, Carleton J, Gordon J . Specificity of P2-purinoceptor that mediates endothelium-dependent relaxation of the pig aorta. Eur J Pharmacol. 1985; 108(3):295-9. DOI: 10.1016/0014-2999(85)90452-2. View

Burnstock G, Kennedy C . Is there a basis for distinguishing two types of P2-purinoceptor?. Gen Pharmacol. 1985; 16(5):433-40. DOI: 10.1016/0306-3623(85)90001-1. View

Houston D, Burnstock G, Vanhoutte P . Different P2-purinergic receptor subtypes of endothelium and smooth muscle in canine blood vessels. J Pharmacol Exp Ther. 1987; 241(2):501-6. View

Pirotton S, Raspe E, Demolle D, Erneux C, Boeynaems J . Involvement of inositol 1,4,5-trisphosphate and calcium in the action of adenine nucleotides on aortic endothelial cells. J Biol Chem. 1987; 262(36):17461-6. View

Hepler J, Earp H, Harden T . Long-term phorbol ester treatment down-regulates protein kinase C and sensitizes the phosphoinositide signaling pathway to hormone and growth factor stimulation. Evidence for a role of protein kinase C in agonist-induced desensitization. J Biol Chem. 1988; 263(16):7610-9. View

Challiss R, Batty I, Nahorski S . Mass measurements of inositol(1,4,5)trisphosphate in rat cerebral cortex slices using a radioreceptor assay: effects of neurotransmitters and depolarization. Biochem Biophys Res Commun. 1988; 157(2):684-91. DOI: 10.1016/s0006-291x(88)80304-8. View

10.

Demolle D, Lagneau C, Boeynaems J . Stimulation of prostacyclin release from aortic smooth muscle cells by purine and pyrimidine nucleotides. Eur J Pharmacol. 1988; 155(3):339-43. DOI: 10.1016/0014-2999(88)90526-2. View

11.

King W, Rittenhouse S . Inhibition of protein kinase C by staurosporine promotes elevated accumulations of inositol trisphosphates and tetrakisphosphate in human platelets exposed to thrombin. J Biol Chem. 1989; 264(11):6070-4. View

12.

Pfeilschifter J, Ochsner M, Whitebread S, de Gasparo M . Down-regulation of protein kinase C potentiates angiotensin II-stimulated polyphosphoinositide hydrolysis in vascular smooth-muscle cells. Biochem J. 1989; 262(1):285-91. PMC: 1133259. DOI: 10.1042/bj2620285. View

13.

Fine J, Cole P, Davidson J . Extracellular nucleotides stimulate receptor-mediated calcium mobilization and inositol phosphate production in human fibroblasts. Biochem J. 1989; 263(2):371-6. PMC: 1133439. DOI: 10.1042/bj2630371. View

14.

Davidson J, Wakefield I, Sohnius U, van der Merwe P, Millar R . A novel extracellular nucleotide receptor coupled to phosphoinositidase-C in pituitary cells. Endocrinology. 1990; 126(1):80-7. DOI: 10.1210/endo-126-1-80. View

15.

Davis P, Hill C, Keech E, Lawton G, Nixon J, Sedgwick A . Potent selective inhibitors of protein kinase C. FEBS Lett. 1989; 259(1):61-3. DOI: 10.1016/0014-5793(89)81494-2. View

16.

Boeynaems J, Pearson J . P2 purinoceptors on vascular endothelial cells: physiological significance and transduction mechanisms. Trends Pharmacol Sci. 1990; 11(1):34-7. DOI: 10.1016/0165-6147(90)90039-b. View

17.

Sim S, Kim J, Rhee S . Regulation of D-myo-inositol 1,4,5-trisphosphate 3-kinase by cAMP-dependent protein kinase and protein kinase C. J Biol Chem. 1990; 265(18):10367-72. View

18.

Allsup D, Boarder M . Comparison of P2 purinergic receptors of aortic endothelial cells with those of adrenal medulla: evidence for heterogeneity of receptor subtype and of inositol phosphate response. Mol Pharmacol. 1990; 38(1):84-91. View

19.

Pfeilschifter J . Comparison of extracellular ATP and UTP signalling in rat renal mesangial cells. No indications for the involvement of separate purino- and pyrimidino-ceptors. Biochem J. 1990; 272(2):469-72. PMC: 1149723. DOI: 10.1042/bj2720469. View

20.

Smrcka A, Hepler J, Brown K, Sternweis P . Regulation of polyphosphoinositide-specific phospholipase C activity by purified Gq. Science. 1991; 251(4995):804-7. DOI: 10.1126/science.1846707. View