Histidine-containing dipeptides as endogenous regulators of the activity of sarcoplasmic reticulum Ca-release channels.
It is shown that histidine-containing dipeptide carnosine (beta-alanyl-L-histidine), which is present in skeletal muscles in millimolar concentrations, decreases the rate of Ca2+ accumulation by the heavy fraction of sarcoplasmic reticulum from rabbit skeletal muscles. This effect results from the ability of carnosine to induce a rapid Ca2+ release from the heavy sarcoplasmic reticulum vesicles via activation of the ruthenium red-sensitive Ca-channels. The effect of carnosine is dose-dependent that indicates the presence of saturable site(s) for carnosine in the molecules of Ca-channels. The C0.5 value carnosine (the concentration that induces the half-maximal Ca2+ release) is 8.7 mM. The 1 N-methylated derivative of carnosine, i.e., anserine, also induces a rapid Ca2+ release with the half-maximal effect at 2.7 mM. Conversely, neither histidine nor beta-alanine (both separately and in the mixture) cause Ca2+ release. In addition, carnosine increases the sensitivity of Ca-channels to their well-known activators (caffeine, AMP, and Ca2+) and decreases inhibitory effect of low concentrations of Mg2+. It is concluded that carnosine as a component of skeletal muscles can be an endogenous regulator of the sarcoplasmic reticulum Ca-channel activity.
Batrukova
M A
MA
Department of Biochemistry, School of Biology, M.V. Lomonosov Moscow State University, Russia.
Rubtsov
A M
AM
D000249:Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002336:Carnosine / Q000494:pharmacology*; D006639:Histidine; D007425:Intracellular Membranes / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000378:metabolism; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D015220:Calcium Channels; D002110:Caffeine; D000249:Adenosine Monophosphate; D006639:Histidine; D002336:Carnosine; D008274:Magnesium; D002118:Calcium