Effects of d-tubocurarine on rat cardiac muscarinic receptors: a comparison with gallamine.
Gallamine and d-tubocurarine inhibited (3H)N-methyl-scopolamine [3H)NMS) binding to rat cardiac muscarinic receptors with I50 values of 0.7 microM and 22 microM, respectively. They decreased the association and dissociation rates of the two ligands (3H)NMS and (3H)Oxotremorine M [3H)Oxo-M). Gallamine interaction with muscarinic receptors was markedly inhibited by (3H)NMS and (3H)Oxo-M binding to the receptors. We were unable to demonstrate (3H)NMS or (3H)Oxo-M binding to the muscarinic receptor-gallamine complex. By contrast, d-tubocurarine interaction with rat cardiac muscarinic receptors was facilitated by (3H)Oxo-M binding and only slightly inhibited by (3H)NMS binding to muscarinic binding sites. Furthermore, (3H)NMS and (3H)Oxo-M bound to the receptor-d-tubocurarine complex, indicating that the latter drug interacted with an allosteric site on cardiac muscarinic receptors but did not recognize the muscarinic binding site (at concentrations below 1 mM).
Waelbroeck
M
M
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
Robberecht
P
P
De Neef
P
P
Christophe
J
J
D000818:Animals; D001667:Binding, Competitive; D005703:Gallamine Triethiodide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D019832:N-Methylscopolamine; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012602:Scopolamine Derivatives / Q000378:metabolism; D014403:Tubocurarine / Q000494:pharmacology*
D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D005703:Gallamine Triethiodide; D019832:N-Methylscopolamine; D014403:Tubocurarine