The excitation-contraction coupling on C2C12 skeletal muscle myotubes was modulated by NO-donor ester of gemfibrozil.
The excitation-contraction coupling in skeletal muscle is modulated by nitric oxide via redox status modification of ryanodine receptor on sarcoplasmic reticulum during events that lead to muscle contraction. We have synthesized a derivative of antilipidemic drug, gemfibrozil, in which a NO-donor furoxan moiety is joined to the fibrate by an ester linkage. Aim of the present study was to determine if the NO released from the above compound is capable of influencing the NO-sensible E-C coupling steps in skeletal muscle and if this effect could be potentially utilised for physiopathological studies and pharmaceutical applications. To obtain this goal we decided to study some of the excitation-contraction mechanisms in the presence of NO-releasing derivative of gemfibrozil in skeletal muscle C2C12 cell line.
Maccallini
Cristina
C
Dipartimento di Scienze del Farmaco, Università degli Studi G.d'Annunzio Chieti-Pescara, via Dei Vestini, 29, I-66013 Chieti, Italy.
Pietrangelo
Tiziana
T
Mancinelli
Rosa
R
Amoroso
Rosa
R
Bettoni
Giancarlo
G
Fulle
Stefania
S
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015248:Gemfibrozil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
C532147:3-((5-oxido-4-phenylsulfonyl-1,2,5-oxadiazol-3-yl)oxy)propyl 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoate; D004952:Esters; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D009569:Nitric Oxide; D015248:Gemfibrozil