Displacement of [3H]oxotremorine-M binding by muscarinic antagonists in guinea-pig atrial and ileal membrane homogenates.
Displacement of [3H]oxotremorine-M [( 3H]oxo-M) binding by muscarinic antagonists that are functionally non-selective (atropine), ileoselective (4-DAMP) or cardioselective (gallamine, pancuronium, vecuronium, himbacine) was investigated in guinea-pig atrial and ileal longitudinal muscle membranes. [3H]Oxo-M bound to a single population of high affinity sites in atrial (KD = 11.40 nM) and ileal (KD = 6.15 nM) membranes. Atropine displaced [3H]oxo-M binding sites in a competitive manner, showing similar affinities in the two tissues. 4-DAMP showed two binding sites in ileum but not in atria. The dissociation constant at the high affinity site in ileum was ca 5-fold lower than the value observed in atria, indicating ileoselectivity. Vecuronium also displaced [3H]oxo-M binding in a competitive manner and exhibited similar affinities in both tissues. Gallamine, pancuronium and himbacine displayed two binding sites in each of the two tissues with the majority of sites (ca. 60-80%) showing high affinity. Overall the cardioselective antagonists do not exhibit any consistent correlation between the affinities found in functional experiments and those determined in binding experiments.
Choo
L K
LK
School of Pharmacology, Victorian College of Pharmacy, Parkville, Victoria, Australia.
Mitchelson
F
F
D000818:Animals; D001285:Atropine / Q000378:metabolism; D001667:Binding, Competitive; D005260:Female; D005703:Gallamine Triethiodide / Q000378:metabolism; D006168:Guinea Pigs; D006325:Heart Atria / Q000378:metabolism; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010095:Oxotremorine / Q000031:analogs & derivatives* / Q000378:metabolism; D010276:Parasympatholytics / Q000378:metabolism*; D010880:Piperidines / Q000378:metabolism
D010276:Parasympatholytics; D010880:Piperidines; D010095:Oxotremorine; C042743:oxotremorine M; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D005703:Gallamine Triethiodide