Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P20020 (
adenosine triphosphatase
)
3,299
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Thyroid hormones influence the function of many organs and mediate their diverse actions through two types of thyroid hormone receptors, TRalpha and TRbeta. Little is known about effects of ligands that preferentially interact with the two different TR subtypes. In the current study the comparison of the effects of the novel synthetic TRbeta-selective compound
GC-1
with T3 at equimolar doses in hypothyroid mice revealed that
GC-1
had better triglyceride-lowering and similar cholesterol-lowering effects than T3. T3, but not
GC-1
, increased heart rate and elevated messenger RNA levels coding for the I(f) channel (HCN2), a cardiac pacemaker that was decreased in hypothyroid mice. T3 had a larger positive inotropic effect than
GC-1
. T3, but not
GC-1
, normalized heart and body weights and messenger RNAs of myosin heavy chain alpha and beta and the sarcoplasmic reticulum
adenosine triphosphatase
(Serca2). Additional dose-response studies in hypercholesteremic rats confirmed the preferential effect of
GC-1
on TRbeta-mediated parameters by showing a much higher potency to influence cholesterol and TSH than heart rate. The preferred accumulation of
GC-1
in the liver vs. the heart probably also contributes to its marked lipid-lowering effect vs. the absent effect on heart rate. These data indicate that
GC-1
could represent a prototype for new drugs for the treatment of high lipid levels or obesity.
...
PMID:The thyroid hormone receptor-beta-selective agonist GC-1 differentially affects plasma lipids and cardiac activity. 1096 73
