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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Harris, G. C. Eglen, R. M. |
| Description | Author Affiliation: Eglen RM ( Institute of Pharmacology, Syntex Discovery Research, Palo Alto, CA 94304.) |
| Abstract | 1. The role of muscarinic M2 and M3 receptors in ileal smooth muscle has been evaluated by use of selective receptor alkylation. The alkylating agents, 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine (4-DAMP mustard) was studied for effects against (+)-cis-dioxolane, at muscarinic M2 and M3 receptors in guinea-pig atria or ileum, respectively. 4-DAMP mustard (10 nM, 40 min exposure) did not discriminate between these muscarinic receptors. In ileum, 4-DAMP mustard, at 100 nM, resulted in a large dextral shift (197 fold) and depression in maxima. In atria there was a smaller dextral shift (14 fold) but no depression in maxima. 2. The muscarinic antagonists, atropine (non-selective), methoctramine (M2-selective) and para-fluorohexahydro-siladiphenidol (pFHHSiD; M3 selective) were studied in protection studies against alkylation by phenoxybenzamine. Washout studies following equilibration of the tissues with atropine (30 nM), methoctramine (0.3 microM) or pFHHSiD (3 microM), showed the compounds to be reversible. No temporal changes in sensitivity to (+)-cis-dioxolane were observed. 3. Exposure, for 20 min, of atria and ileum to phenoxybenzamine (3 and 10 microM respectively) caused dextral shifts and depressions in the maxima of the concentration-response curve to (+)-cis-dioxolane. These effects were inhibited by prior equilibration with atropine (30 nM) and methoctramine (0.1 microM) in atria or atropine (30 nM) and pFHHSiD (3 microM) in ileum. Similar results in ileum were obtained when pilocarpine was used as the agonist. 4. These data were consistent with muscarinic M2 receptors mediating responses in atria and M3 receptors mediating responses in ileum. No evidence was provided for a direct role of muscarinic M2 receptors in ileal contraction.5. It is concluded that receptor protection by reversible antagonists for muscarinic M2 or M3 receptors provides a means to isolate pharmacologically a single subtype in a tissue possessing heterogeneous populations. This technique may prove useful in defining the role of the respective subtypes in smooth muscle contraction. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 109 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1993-08-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Heart Drug Effects Muscarinic Antagonists Muscle, Smooth Alkylating Agents Pharmacology Animals Atropine Diamines Dioxolanes Diphenylacetic Acids Guinea Pigs Heart Atria Ileum In Vitro Techniques Isometric Contraction Parasympatholytics Phenoxybenzamine Antagonists & Inhibitors Pilocarpine Piperidines Receptors, Muscarinic |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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