Abstract
When rat astrocytes in primary culture were incubated with bradykinin, inositol phosphate formation and arachidonic acid release were stimulated.
By themselves, phorbol esters inhibited inositol phosphate formation, but phorbol esters and other cell-permeant diacylglycerol analogues stimulated arachidonic acid release. Preincubation of the cells with phorbol esters or diacylglycerol analogues blocked bradykinin-stimulated inositol phosphate formation but augmented bradykinin-stimulated arachidonic acid release.
The present results suggest that, in astrocytes, bradykinin activates at least two signal transduction pathways bradykinin stimulates a phosphatidylinositol-specific phospholipase C leading to enhanced inositol phosphate formation, and bradykinin stimulates a second phospholipase to enhance arachidonic acid release. The pathways may be distinguished using phorbol esters and other diacylglycerol mimetics.
The possibility is raised that diacylglycerol, formed in response to bradykinin, may serve as a transducer of receptor-receptor interactions by altering the ability of receptors to stimulate phospholipase activity.
Key words: phospholipases, phospholipase C, arachidonic acid, bradykinin, phorbol esters, protein kinase C, astrocytes
References
- Berridge, M. J. (1984). Inostiol trisphosphate and diacylglycerol as second messengers.Biochem. J.220345–360. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berridge, M. J., Downes, C. P., and Hanley, M. R. (1982). Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands.Biochem. J.206587–595. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burch, R. M. (1987). Endotoxin and zymosan-induced prostaglandin synthesis are mediated by protein kinase C in macrophases.Eur. J. Pharmacol.142431–435. [DOI] [PubMed] [Google Scholar]
- Burch, R. M., and Axelrod, J. (1987). Dissociation of bradykinin-induced prostaglandin synthesis from inositol phosphate formation in Swiss 3T3 cells. Evidence for G protein regulation of phospholipase A2.Proc. Natl. Acad. Sci. USA846374–6378. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burch, R. M., Ma, A. L., and Axelrod, J. (1988). Phorbol esters and diglycerides amplify bradykinin-stimulated prostaglandin synthesis in Swiss 3T3 fibroblasts.J. Biol. Chem. (in press). [PubMed]
- Duman, R. S., Karbon, E. W., Harrington, C., and Enna, S. J. (1986). An examination of the involvement of phospholipases A2 and C in the alpha-adrenergic and gamma-aminobutyric acid receptor modulation of cyclic AMP accumulation in rat brain slices.J. Neurochem.47801–810. [DOI] [PubMed] [Google Scholar]
- Evans, T., McCarthy, K. D., and Harden, T. K. (1984). Regulation of cyclic AMP accumulation by peptide hormone reaceptors in immunocytochemically defined astroglial cells.J. Neurochem.43131–138. [DOI] [PubMed] [Google Scholar]
- Francel, P. C., Miller, R. J., and Dawson, G. (1987). Modulation of bradykinin-induced inositol trisphosphate release in a novel neuroblastoma × dorsal root ganglion sensory neuron cell line (F-11).J. Neurochem.481632–1639. [DOI] [PubMed] [Google Scholar]
- Irvine, R. (1982). How is the level of free arachidonate maintained in cells?Biochem. J.2043–16.6810878 [Google Scholar]
- Jeremy, J. Y., and Dandona, P. (1987). Involvement of protein kinase C in alpha adrenergic stimulation of prostaglandin synthesis.Eur. J. Pharmacol.136311–316.3111864 [Google Scholar]
- Leeb-Lundberg, L. M. F., Cotecchia, S., Lomasney, J. W., DeBernardis, J. F., Lefkowitz, R. J., and Caron, M. G. (1985). Phorbol esters promote alpha1-adrenergic receptor phosphorylation and receptor uncoupling from inositol phospholipid metabolism.Proc. Natl. Acad. Sci. USA825651–5655. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCarthy, K. D. (1983). An autoradiographic analysis of beta-adrenergic receptors on immunocytochemically defined astroglia.J. Pharmacol. Exp. Ther.226282–290. [PubMed] [Google Scholar]
- McCarthy, K. D., and de Vellis, J. (1980). Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue.J. Cell Biol.85890–902. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meyer, R. A., and Campbell, J. N. (1981). Myelinated nociceptive afferents account for the hyperalgesia that follows a burn to the hand.Science2131527–1529. [DOI] [PubMed] [Google Scholar]
- Niedel, J. E., and Blackshear, P. J. (1987). Protein kinase C. InReceptor Biochemistry and Methodology, Vol. 7. Phosphoinositides and Receptor Mechanisms (J. W. Putney, Ed.), Alan R. Liss, New York, pp. 47–88. [Google Scholar]
- Nishizuka, Y. (1984). The role of protein kinase C in signal transduction and tumor promotion.Nature308693–698. [PubMed] [Google Scholar]
- Raff, M. C., Fields, K. L., Hakomori, S.-I., Mirsky, R., Pruss, R. M., and Winter, J. (1979). Cell-type-specific markers for distinguishing and studying neurons and the major classes of glial cells in culture.Brain Res.174283–308. [DOI] [PubMed] [Google Scholar]
- Ransom, B. R., Neale, E., Henkart, M., Bullock, P. N., and Nelson, P. G., (1977). Mouse spinal cord in cell culture. I. Morphology and intrinsic neuronal electrophysiologic properties.J. Neurophysiol.401132–1150. [DOI] [PubMed] [Google Scholar]
- Regoli, D., and Barabe, J. (1980). Pharmacology of bradykinin and related kinins.Pharmacol. Rev.321–46. [PubMed] [Google Scholar]
- Sherman, W. R., Leavitt, A. L., Honchar, M. P., Hallacher, L. M., and Phillips, B. E. (1981). Evidence that lithium alters phosphoinositide metabolism: Chronic administration elevates primarily D-myo-inositol-1-phosphate in cerebral cortex of the rat.J. Neurochem.361947–1951. [DOI] [PubMed] [Google Scholar]
- Vanacek, J., Sigden, D., Weller, J. L., and Klein, D. C. (1986). See-saw signal processing in pinealocytes involves reciprocal changes in the alpha1-adrenergic component of the cyclic GMP response and the beta-adrenergic component of the cyclic AMP response.J. Neurochem.47678–686. [DOI] [PubMed] [Google Scholar]
- Watson, S. P., and Lapetina, E. G. (1985). 1,2,-Diacylglycerol and phorbol ester inhibit agonistinduced formation of inositol phosphates in human platelets: Possible implications for negative feedback regulation of inositol phospholipid hydrolysis.Proc. Natl. Acad. Sci. USA822623–2626. [DOI] [PMC free article] [PubMed] [Google Scholar]