A comparison of the affinities of antagonists for acetylcholine receptors in the ileum, bronchial muscle and iris of the guinea-pig.
1. Isolated preparations of bronchial strip and of intact iris from the guineapig have been adapted for the measurement of affinity constants of substances which block post-ganglionic acetylcholine receptors.2. The affinity constants of 28 compounds on bronchial muscle and of 8 compounds on the iris have been compared with values measured on the guinea-pig ileum.3. Although the compounds differed up to a million-fold in affinity, most of the estimates of log affinity constant for the bronchial muscle and iris differed only slightly from those on the ileum.4. Some of the differences could be attributed to the actions of hexamethonium, used in the tests on the ileum but not, initially, in the tests with the bronchial strip and iris. Hexamethonium reduced most of the estimates of log K for the receptors in the bronchial strip by a variable but significant amount, which could be due, at least in part, to a weak post-ganglionic blocking (atropine-like) action. On average, hexamethonium had little effect on the estimates made with the ileum, appreciably decreasing estimates with some compounds and increasing those with others.5. The results indicate that, although there may be differences between the acetylcholine receptors in the three types of tissue, there is no conclusive evidence, because the differences in affinity which we have observed could have arisen from differences in the experimental conditions. This is illustrated by results obtained with the guinea-pig ileum recorded with the same technique as was used for the bronchial strip, which are presented as an appendix.6. Such differences as may exist between these three types of acetylcholine receptor are likely to be limited to the replacement of one aminoacid in the receptor protein by a homologue.
D000109:Acetylcholine / Q000037:antagonists & inhibitors*; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002415:Cats; D005730:Ganglionic Blockers / Q000494:pharmacology; D006168:Guinea Pigs; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007498:Iris / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011950:Receptors, Cholinergic; D011955:Receptors, Drug
D005730:Ganglionic Blockers; D006584:Hexamethonium Compounds; D011950:Receptors, Cholinergic; D011955:Receptors, Drug; D002217:Carbachol; D000109:Acetylcholine