Diabetic state-induced modifications of succinylcholine binding mode in the microsomal fractions of mouse skeletal muscles.
The skeletal muscles of alloxan-induced diabetic mice and genetically diabetic KK-CAY mice are hypersensitive to a depolarizing blocker, succinylcholine (SuCh) but not to the competitive antagonist, d-tubocurarine (d-TC). The mechanism by which the action of the depolarizing blocker is modified in the diabetic state was investigated on the binding of 14C-SuCh to the microsomal fraction isolated from mouse skeletal muscles. The Scatchard plot of microsomal preparations from normal ddY mice showed positive cooperativity in SuCh binding, whereas that of the preparations from alloxan-induced diabetic mice as well as genetically diabetic KK-CAY mice lost the positive cooperative interactions. The dissociation constant (Kd) of high affinity site in diabetic muscles was significantly lower than that in non-diabetic ddY muscle. The microsomal fractions from denervated muscles of normal ddY mice maintained weakly positive cooperativity in SuCh binding, and the affinity of SuCh binding in denervated muscles was lower than that of non-denervated muscles. In conclusion, the diabetic state selectively altered the SuCh binding mode. This alteration seems to be closely correlated with the pharmacological hypersensitivity to SuCh.
Kimura
M
M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Kimura
I
I
Fujihara
M
M
Hoshino
N
N
D000496:Alloxan; D000818:Animals; D001665:Binding Sites; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D013390:Succinylcholine / Q000378:metabolism*
D000496:Alloxan; D013390:Succinylcholine