Differential allosteric effects of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate-HCl (TMB-8) on muscarinic receptor subtypes.
TMB-8, a putative inhibitor of intracellular calcium mobilization, prevents the binding of the muscarinic ligand N-[3H]methylscopolamine. The inhibition was observed in four tissues from guinea pig; cortex, heart, pancreas, and ileum, representing M1, cardiac M2, glandular M2, and heterogeneous M2 subtypes of muscarinic receptors, respectively. The Ki values for all four tissues were approx. 4 microM. However, dissociation kinetics revealed that TMB-8 interacted with an allosteric site of three muscarinic receptor subtypes but not the subtype from pancreas. These results indicate that TMB-8 interacts with muscarinic receptors, and therefore would disrupt calcium mobilization or any second messenger system coupled to these receptors.
Gordon
R K
RK
Department of Applied Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Chiang
P K
PK
D000494:Allosteric Regulation; D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D005707:Gallic Acid / Q000378:metabolism / Q000494:pharmacology / Q000031:analogs & derivatives; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000145:classification / Q000187:drug effects*
D011976:Receptors, Muscarinic; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid