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Membrane Phospholipid Metabolism and Transmitters

  • Chapter
Receptor-Receptor Interactions

Part of the book series: Wenner-Gren Center International Symposium Series ((WGS))

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Abstract

Many neurotransmitters are now known to act by using a ubiquitous signal transduction mechanism based on the hydrolysis of a unique lipid (Downes, 1983; Nahorski et al, 1986). The lipid in question is phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P2) located within the inner leaflet of the plasma membrane where it is stored as a precursor to be used by the receptor mechanism to generate second messengers (Downes & Michell, 1985; Berridge, 1984; Berridge & Irvine, 1984). The transmitters known to operate through this inositol lipid mechanism include acetylcholine (muscarinic), norepinephrine (α1), histamine (H1), 5-hydroxytryptamine (5-HT2), vasopressin (V1), substance P, bradykinin, neurotensin and glutamate. Upon binding its appropriate transmitter, the receptor operates through a GTP-binding protein (Gp) which activates a phosphoinositidase to cleave PtdIns4,5P2 at its phosphodiester bond to release inositol 1,4,5-trisphosphate (Insl,4,5P3) which diffuses into the cytosol leaving diacylglycerol (DG) behind in the membrane. This hydrolysis of PtdIns4,5P2 is a key event in signal transduction because both products give rise to second messengers and thus represents a bifurcation in the signal pathway. The DG functions by stimulating protein kinase C (C-kinase) (Nishizuka, 1986) whereas Ins1,4,5P3 mobilizes calcium (Berridge, 1984; Berridge & Irvine, 1984). In this article I shall attempt to describe how the dual signalling system based on the DG/C-kinase and Ins1,4,5P3/calcium pathways might participate in the control of neural activity. Particular attention will be paid to the role of the DG/C-kinase pathway in carrying our receptor-receptor interactions. Such transmodulation of receptor activity represents one of the major functions of protein kinase C.

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  1. M. J. Berridge
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Editors and Affiliations

  1. Department of Histology, Karolinska Institutet, Stockholm, Sweden

    Kjell Fuxe

  2. Department of Human Physiology, University of Modena, Modena, Italy

    Luigi F. Agnati

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© 1987 The Wenner-Gren Center

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Berridge, M.J. (1987). Membrane Phospholipid Metabolism and Transmitters. In: Fuxe, K., Agnati, L.F. (eds) Receptor-Receptor Interactions. Wenner-Gren Center International Symposium Series. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-08949-9_13

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