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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Dowling, Mark R. Mistry, Rajendra Challiss, R. A. John |
| Description | Author Affiliation: Mistry R ( Department of Cell Physiology and Pharmacology, University of Leicester, Maurice Shock Medical Sciences Building, University Road, Leicester.) |
| Abstract | 1. A range of muscarinic acetylcholine (mACh) receptor agonists (methacholine (MCh), oxotremorine-M (OXO-M), oxotremorine (OXO), arecoline (AREC), bethanechol (BETH), pilocarpine (PILO)) have been investigated with respect to their binding to, and activation of, M(2) and M(4) mACh receptors, recombinantly expressed in Chinese hamster ovary cells, to explore the possibility that these agonists may differentially affect mACh receptor-G(i/o) and -G(s) coupling. 2. M(2)/M(4) mACh receptor coupling to the adenylyl cyclase/cyclic AMP signalling pathway has been explored in intact cells. G(i/o)-mediated negative coupling to adenylyl cyclase was explored functionally by assessing the ability of the mACh receptor agonists to inhibit forskolin-stimulated enzymic activity. Following pertussis toxin treatment (100 ng ml(-1), 18-20 h) to inactivate G(i/o) proteins, each agonist caused a G(s)-mediated enhancement of forskolin-stimulated adenylyl cyclase activity. 3. At both M(2) and M(4) mACh receptors, all agonists tested were more potent in mediating G(i/o)- versus G(s)-coupled responses. This difference (determined as the pIC(50) (G(i/o) coupling) minus pEC(50) (G(s) coupling) value) was greatest for AREC (65-75-fold) and least for BETH and PILO ( |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 144 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2005-02-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | GTP-Binding Protein Alpha Subunits, Gi-Go Metabolism GTP-Binding Protein Alpha Subunits, Gs Muscarinic Agonists Pharmacology Receptor, Muscarinic M2 Agonists Receptor, Muscarinic M4 Signal Transduction Drug Effects Animals Binding, Competitive CHO Cells Cricetinae Cricetulus Recombinant Proteins Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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