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: EC:3.6.3.44 (
P-glycoprotein
)
13,344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
ABC-type transport proteins, such as
P-glycoprotein
(
P-gp
), modify intracellular concentrations of many substrate compounds. They serve as functional barriers against entry of xenobiotics (e.g., in the gut or the blood-brain barrier) or contribute to drug excretion. Expression of transport proteins in the heart could be an important factor modifying cardiac concentrations of drugs known to be transported by
P-gp
(e.g., beta-blockers, cardiac glycosides, doxorubicin). We therefore investigated the expression and localization of
P-gp
in human heart. Samples from 15 human hearts (left ventricle; five non-failing, five
dilated cardiomyopathy
, and five ischemic cardiomyopathy) were analyzed for expression of
P-gp
using real-time RT-PCR, immunohistochemistry, and in situ hybridization. Immunohistochemistry revealed expression of
P-gp
in endothelium of both arterioles and capillaries of all heart samples. Although
P-gp
mRNA was detected in all samples, its expression level was significantly reduced in patients with
dilated cardiomyopathy
. We describe variable expression of
P-gp
in human heart and its localization in the endothelial wall. Thus, intracardiac concentrations of various compounds may be modified, depending on the individual
P-gp
level.
...
PMID:Expression and localization of P-glycoprotein in human heart: effects of cardiomyopathy. 1236 68
Members of the ATP-binding cassette (ABC) protein superfamily are integral membrane proteins involved in energy-dependent transport of a wide variety of substrates across biologic membranes. ATP-binding cassette transporters serve as functional barriers against the entry of xenobiotics, for example, in the intestine or at the blood-brain barrier, or contribute to drug excretion, for example, in the kidney or the liver. Many human ABC transporters, such as ABCB1 (
P-glycoprotein
), ABCC5 (MRP5), or ABCC9 (SUR2), are expressed in the heart, suggesting an important role of these transporters in cardiac drug effects or physiology. Interestingly, mutations in ABCC9, a constituent of cardiac K(ATP) channels, can cause
dilated cardiomyopathy
in humans, providing evidence that dysfunction of cardiac ABC transporters might have clinical implications. This review aims to give insights into the possible functions of ABC transporters in the heart, their role in drug disposition, as well as control of intracellular cyclic nucleotide levels or regulation of K(ATP) channel conductivity.
...
PMID:ATP-binding cassette transporters in the heart. 1638 24
