Pr. Warnick et al., RABBIT SKELETAL-MUSCLE SARCOPLASMIC-RETICULUM CA2-ATPASE ACTIVITY - STIMULATION IN-VITRO BY THYROID-HORMONE ANALOGS AND BIPYRIDINES(), Biochimica et biophysica acta, 1153(2), 1993, pp. 184-190
Sarcoplasmic reticulum-enriched membranes from rabbit skeletal muscle
contained Ca2+-ATPase activity which was significantly enhanced (26% i
ncrease, P<0.001) in vitro by physiological concentrations (10(-10) M)
of L-thyroxine (T-4) and 3,3',5-triiodo-L-thyronine (T-3). In contras
t, the biologically inactive iodothyronine analogues D-T-4 and 3,3',5,
5'-tetraiodothyroacetic acid (Tetrac) (10(-10) M) were without effect
on enzyme activity. 3,5-Dimethyl-3'-isopropyl-L-thyronine (Dimit), a b
ioactive analogue, was highly effective as a Ca2+-ATPase stimulator, i
ncreasing enzyme activity by 43% (P<0.02 vs. T-4 effect). A bipyridine
cardiac inotropic agent, milrinone, has been reported to be thyromime
tic in a myocardial membrane Ca2+-ATPase system, and in concentrations
from 10(-10) to 10(-5) M enhanced skeletal muscle SR membrane Ca2+-AT
Pase activity in vitro (P<0.001). Milrinone analogues which have been
previously shown to enhance rabbit myocardial membrane Ca2+-ATPase act
ivity, and which have a twist relationship of the pyridine rings, were
also striated muscle Ca2+-ATPase stimulators. We conclude that (1) st
riated muscle is a mammalian tissue in which physiological levels of b
iologically relevant thyroid hormone analogues, particularly Dimit, st
imulate Ca2+-ATPase activity in vitro by a non-genomic mechanism; (2)
cardiac bipyridine analogues which are thyromimetic in vitro in rabbit
heart, and which have structural homologies with thyroid hormone, are
stimulators of rabbit striated muscle sarcoplasmic reticulum Ca2+-ATP
ase activity.