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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kenakin, T. |
| Description | Author Affiliation: Kenakin T ( GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA. Terry.P.Kenakin@gsk.com) |
| Abstract | This commentary discusses a paper in this issue by Dr Jillian Baker on the antagonism of histamine H(2) receptors. It is an excellent example of the use of pharmacological principles to determine what systems can and can't do from the point of view of agonist-dependent antagonism. The most common model of antagonism, namely orthosteric, cannot discern agonist type; i.e. all agonists are blocked equally by a given orthosteric antagonist. Therefore, if quantitative assessment of antagonism unveils agonist dependence, then this is something an orthosteric mechanism cannot do and another mechanism must be considered. A simple alternative is a permissive allosteric model whereby the agonist and antagonist interact through conformational changes in the receptor protein. Under these circumstances, an agonist-antagonist dialogue can ensue whereby the nature of the agonist determines the magnitude of antagonist effect. Jillian Baker contrasts antagonist systems with historical data obtained for beta-adrenoceptors and the present data for histamine H(2) receptors where the simpler model of orthosteric antagonism suffices and thus shows how quantitative receptor pharmacology can be used to determine the molecular mechanism of antagonism. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 5 |
| Volume Number | 153 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2008-03-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Drug Agonism Drug Antagonism Allosteric Site Physiology Histamine H2 Antagonists Pharmacology Ligands Models, Biological Receptors, Histamine H2 Drug Effects |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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