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Second messenger systems as sites of drug action

Published online by Cambridge University Press:  05 December 2011

W. C. Bowman
W. C. Bowman
Affiliation:
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow G1 1XW, U.K.
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Synopsis:

Transmembrane signalling from cell surface receptors occurs by two broad mechanisms: (i) the rapid (ms) direct opening of an ion channel, where the ion channel is a component of the receptor complex (e.g. the nicotinic acetylcholine receptor); and (ii) the more slow (s) modulation of a membrane enzyme or more distant ion channel. Most of the examples of this second mechanism involve a GTP-binding protein or so–called G-protein, and the production of a second messenger. The production of nitric oxide is a special case in that it is eventually produced as a result of the activity of the second messenger ïnositol trisphosphate. The nitric oxide then diffuses into a second cell to give rise to the production of an additional ‘second’ messenger, cyclic GMP.

All of the surface receptors themselves exist as a number of subtypes. Additionally, most of the components of the second messenger systems – G-proteins, adenylyl cyclase, guanylyl cyclase, phosphoinositidase, C, inositol trisphosphate receptors, protein kinase A, protein kinase G, protein kinase C, cyclic nucleotide phosphodiesterases, and the enzymes involved in phosphatidylinositol resynthesis – occur in a number of isoforms. Furthermore, all the enzymes are controlled in their activity by a number of co-factors and other modulators. This diversity provides the potential for selective drug action, a potential which is already being exploited and which will be increasingly so in the near future.

Type
Research Article
Information
Proceedings of the Royal Society of Edinburgh, Section B: Biological Sciences , Volume 99 , Issue 1-2: The Advancement of Drug Discovery , 1992 , pp. 1 - 17
Copyright
Copyright © Royal Society of Edinburgh 1992

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