Premium
3,5‐ D i‐ t ‐Butylcatechol as a Ryanodine Receptor Agonist in Rat Intact Skeletal Muscle Fibers
Author(s) -
Lacava Caterina,
Sgaragli Giampietro,
Fusi Fabio
Publication year - 2012
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21003
Subject(s) - ryanodine receptor , chemistry , agonist , muscle contraction , contraction (grammar) , skeletal muscle , pharmacology , caffeine , stimulation , endoplasmic reticulum , medicine , diaphragm (acoustics) , endocrinology , receptor , biochemistry , physics , acoustics , loudspeaker
trategy, Management and Health Policy Enabling Technology, Genomics, Proteomics Preclinical Research Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics Clinical Development Phases I‐III Regulatory, Quality, Manufacturing Postmarketing Phase IV3,5‐ D i‐ t ‐butylcatechol ( DTCAT ) stimulates the rat skeletal muscle sarcoplasmic reticulum ryanodine receptor ( RyR ). In the present study, its effects on the contractile response of diaphragm preparation were characterized using electrically stimulated phrenic nerve–diaphragm preparations and diaphragm strips. DTCAT reduced, concentration‐dependently, twitch contraction of the phrenic nerve–diaphragm preparation evoked by both direct and indirect stimulation and increased spontaneous tone. Twitch amplitude reduction was irreversible, while the increase of spontaneous tone was only partially reversible upon DTCAT washout. In diaphragm strips, caffeine > 4‐chloro‐ m ‐cresol >> 3,5‐diisopropylcatechol ≅ ryanodine > DTCAT enhanced spontaneous tone, whereas quercetin reduced it with all the compounds reducing twitch amplitude. DTCAT ‐induced contracture was partly dependent on extracellular Ca 2+ influx and antagonized by a Cd 2+ / La 3+ mixture. In intact skeletal muscle preparations, DTCAT behaved as a RyR agonist.