Inhibition of unloaded shortening velocity in permeabilized muscle fibres by caged ATP compounds.
The effects of both the P3-1-(2-nitrophenyl)ethyl ester of adenosine 5'-triphosphate (NPE-caged ATP) and its separate diastereoisomers, and the P3-3',5'-dimethoxybenzoin ester of ATP (DMB-caged ATP) were studied on the unloaded shortening velocity of glycerinated rabbit psoas muscle fibres. The unloaded shortening velocities of the active fibres were measured as a function of ATP concentration (0.1-5 mM) using the 'slack-test' with and without 2 mM caged ATP. Shortening velocity followed a Michaelis-Menten relationship with ATP concentration, the Km for ATP being 170 microM. The caged ATP compounds inhibited shortening velocity, in a manner consistent with competitive inhibition, with a Ki of 1-2 mM. The R- and S-diastereoisomers of NPE-caged ATP showed the same degree of competitive inhibition of the shortening velocity, as did DMB-caged ATP. These observations suggest that caged ATP compounds bind to the ATPase site of the actomyosin where they compete with the substrate, Mg2+ ATP.
Thirlwell
H
H
National Institute for Medical Research, Mill Hill, London, UK.
Sleep
J A
JA
Ferenczi
M A
MA
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D004548:Elasticity; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000502:physiology; D016658:Psoas Muscles / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D013237:Stereoisomerism; D016474:Weight-Bearing
C092828:P(3)-3',5'-dimethoxybenzoin adenosine-5'-triphosphate; C029273:P(3)-1-(2-nitro)phenylethyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate