Two allosteric modulators interact at a common site on cardiac muscarinic receptors

John Ellis, M. Seidenberg

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

The abilities of gallamine, obidoxime, tetrahydroaminoacridine (THA), and 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) to alter the rate of dissociation of N-[3H]methylscopolamine from rat cardiac muscarinic receptors were investigated. All four ligands monotonically slowed the dissociation, with the order of potency gallamine > TMB-8 > THA > obidoxime. There was a dramatic difference in the efficacy of these allosteric modulators. Gallamine, TMB-8, and THA slowed the dissociation of N- methylscopolamine by >90% at maximally effective concentrations, whereas obidoxime was capable of slowing it by only about 50%. In a manner analogous to the action of a partial agonist, obidoxime was able to partially reverse the effects of the other three modulators. Furthermore, the concentration- dependent effects of combinations of obidoxime and gallamine were in good agreement with the model of competitive interaction between these two ligands. These results provide the first evidence that two muscarinic allosteric modulators interact competitively at a well defined site.

Original languageEnglish (US)
Pages (from-to)638-641
Number of pages4
JournalMolecular Pharmacology
Volume42
Issue number4
StatePublished - 1992

All Science Journal Classification (ASJC) codes

  • Pharmacology

Fingerprint Dive into the research topics of 'Two allosteric modulators interact at a common site on cardiac muscarinic receptors'. Together they form a unique fingerprint.

Cite this