Thienylhydrazone derivative increases sarcoplasmic reticulum Ca2+ release in mammalian skeletal muscle.
3,4-Methylenedioxybenzoyl-2-thienylhydrazone (L-294) is a cardiac inotropic drug whose action is mediated by an increase in intracellular Ca(2+) concentration as a result of enhanced Ca(2+) accumulation in the sarcoplasmic reticulum. In the present study we tested whether this new thienylhydrazone derivative was effective in mammalian skeletal muscle. We investigated the effect of L-294 on the contractility of isolated skeletal muscle, on Ca(2+) uptake and release by sarcoplasmic reticulum in skinned fibers and in membrane vesicles. L-294 increased in a dose-dependent manner tension of isolated rat soleus muscle. In skinned type I fibers, L-294 induced tension and did not alter sarcoplasmic reticulum loading with Ca(2+). L-294 reduced the threshold Ca(2+) to induce Ca(2+) release and did not affect the ATP-dependent accumulation of Ca(2+) by sarcoplasmic reticulum vesicles. These results suggest that L-294 is an inotropic agent in skeletal muscle through an increase in the amount of Ca(2+) released from the sarcoplasmic reticulum.
Zapata-Sudo
Gisele
G
Departamento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco J, Sala 14, Rio de Janeiro 21941-590, Brazil. gsudo@farmaco.ufrj.br
Sudo
Roberto T
RT
Maronas
Patricia A
PA
Silva
Gisele L M
GL
Moreira
Orlando R
OR
Aguiar
Marli I S
MI
Barreiro
Eliezer J
EJ
D000293:Adolescent; D000328:Adult; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D013552:Swine
D006835:Hydrazones; D002118:Calcium