Abstract
Challenge of a variety of different cell types by receptor agonists capable of stimulating adenylate cyclase leads to a transient increase in the intracellular concentrations of cyclic AMP. In hepatocytes, glucagon achieves just this (fig.1). We show that such an event is determined by the initial rapid activation of adenylate cyclase which is then followed by the activation of a specific cyclic AMP phosphodiesterase and desensitization of adenylate cyclase. These events identify ‘interplay’ or ‘cross-talk’ occurring between two distinct cellular signalling systems.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Anderson, N.G., Kilgour, E. & Houslay, M.D. (1989) Biochem. J. (in press). Subcellular localisation and hormone sensitivity of adipocyte phosphodiesterases
Brooks, D.P., Nutting, D.F., Crofton, J.T. & Share, L. (1989) Diabetes 38, 54–57. Elevated plasma vasopressin levels in diabetic rats.
Cercek, B. & Houslay, M.D. (1982) Biochem. J. 207, 123–132. Submitochondrial localisation and disposition of cyclic AMP-phosphod-iesterases.
Cercek, B., Wilson, S.R. & Houslay, M.D. (1983) Biochem. J. 213, 89–97. Heterogeneity of cyclic AMP-phosphodiesterases in endoplasmiv reticulum.
Gawler, D., Milligan, G., Spiegel, A.M., Unson, C.G. & Houslay, M.D. (1987) Nature (Lond.) 327, 229–232. Abolition of the expression of Gi in diabetes.
Heyworth, C.M. & Houslay, M.D. (1983) Biochem. J. 214, 93–98. Challenge of ehpatoeytes with glucagon triggers the rapid modulation of adenylate cyclase activity in membranes.
Heyworth, C.M., Wallace, A.V. & Houslay, M.D. (1983a) Biochem. J. 214, 99–110 Insulin and glucagon regulate the activation of two cyclic AMP-phosphodiesterases in hepatocytes.
Heyworth, C.M., Hansld, E. & Houslay, M.D. (1983b) Biochem. J. 222, 189–194. IAP blocks glucagon desensitizaticn in intact hepatocytes
Heyworth, C.M., Whetton, A.D., Kinsella, A.R. & Houslay, M.D. (1984a) FEBS Lett. 170, 38–42. TPA inhibits adenylate cyclase activity.
Heyworth, C.M., Wallace, A.V., Wilson, S.R. & Houslay, M.D. (1984b) Biochem. J. 222, 183–187. Insulin-stimulated cyclic AMP-phosphodiesterases
Heyworth, C.M., Whetton, A.D., Wong, S., Martin, B.R. & Houslay, M.D. (1985) Biochem. J. 228, 593–603. Insulin inhibits the cholera toxin catalysed ADP-ribosylation of a 25kDa protein.
Houslay, M.D. (1986) Biochem. Soc. Trans 14, 183–193. Insulin, glucagon and the receptor-mediated control of cyclic AMP metabolism.
Houslay, M.D. & Heyworth, C.M. (1983) Trends Biochem. Sci.8, 449–457. Insulin; in search of a mechanism
Houslay, M.D. & Siddle, K. (1989) Brit. Med. Bull. 45, 264–284. Molecular basis of insulin receptor function.
Houslay, M.D., Gawler, D., Milligan, G. & Wilson, A. (1988) Cellular Signalling 1, 9–22. Multiple defects in the G-protein system of liver plasma membranes from Zucker rats.
Irvine, F.J. & Houslay, M.D. (1988) Biochem. Pharmacol. 37, 2773–2779. Effects of treatment of intact hepatocytes with A23187 on cAMP metabolism
Kilgour, E., Anderson, N.G. & Houslay, M.D. (1989) Biochem. J. 260, 27–36. Activation and phosphorylation of the ‘dense-vesicle’ cyclic AMP phosphodiesterase
Lavan, B.E., Lakey, T. & Houslay, M.D. (1989) Biochem. Pharmacol, (in press) Resolution of soluble cyclic nucleotide phosphodiesterase isoenzymes from rat liver
Murphy, G.J. & Houslay, M.D. (1988) Biochem. J. 249, 543–547. Resensitization of adenylate cyclase.
Murphy, G.J., Hruby, V.J., Trivedi, D., Wakelam, M.J.O. & Houslay, M.D. (1987) Biochem. J. 243, 39–46. Rapid desensitization of adenylate cyclase is a cyclic AMP-independent event.
Murphy, G.J., Gawler, D., Milligan, G., Wakelam, M.J.O, Pyne, N.J. & Houslay, M.D. (1989) Biochem. J. 259, 191–197. Glucagon desensitization does not involve the inhibitory G-protein Gi.
Okajima, F., Tokumitsu, Y., Kondo, Y. & Ui, M. (1987) J. Biol. Chem. 262, 13483–13490. P2-purinergic receptor-mediated events in hepatocytes
Pyne, N.J., Cooper, M.E. & Houslay, M.D. (1987a) Biochem.J. 242, 33–42. Insulin- and glucagon-stimulated ‘dense-vesicle’ phosphodiesterase.
Pyne, N.J., Anderson, N., Lavan, B.E., Milligan, G., Nimmo, H.G. & Houslay, M.D. (1987b) Biochem. J. 248, 897–901. Tissue distribution of cyclic AMP-phosphodiesterases in rat
Pyne, N.J., Cooper, M.E. & Houslay, M.D. (1986) Biochem.J. 234, 325–334. Cytosolic and particulate forms of the cGMP-stimulated cyclic AMP-phosphodiesterase.
Pyne, N.J. & Houslay, M.D. (1988) Biochem. Biophys. Res. Commun. 156, 290–296. An insulin ‘mediator’ preparation stimulates the cGMP-stimulated cyclic AMP- phosphodiesterase.
Pyne, N.J., Murphy, G.J., Milligan, G. & Houslay, M.D. (1989) FEBS Lett. Treatment of intact hepatocytes with either glucagon or TPA causes the phosphorylation and functional inactivation of Gi.
Wakelam, M.J.O., Murphy, G.J., Hruby, V.J. & Houslay, M.D. (1986) Nature (Lond.) 323, 68–71. Activation of two signal transduction systems in hepatocytes by glucagon
Whipps, D.E., Armstron, A.E., Pryor, H.J. & Halestrap, A.P. (1987) Bio chem. J. 241, 835–845. Glucagon effects on inositol phospholipd metabolism.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Plenum Press, New York
About this chapter
Cite this chapter
Houslay, M.D. (1990). ‘Cross-Talk’ and the Regulation of Repatocyte Adenylate Cyclase Activity: Desensitization, G1 and Cyclic AMP Phosphodiesterase Regulation. In: Vanderhoek, J.Y. (eds) Biology of Cellular Transducing Signals. GWUMC Department of Biochemistry Annual Spring Symposia. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0559-0_15
Download citation
DOI: https://doi.org/10.1007/978-1-4613-0559-0_15
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4612-7866-5
Online ISBN: 978-1-4613-0559-0
eBook Packages: Springer Book Archive