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:6.3.2.19 (
ubiquitin-protein ligase
)
799
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
G
q/11
protein-coupled human histamine H
1
receptors in Chinese hamster ovary cells stimulated with histamine undergo clathrin-dependent endocytosis followed by proteasome/lysosome-mediated down-regulation. In this study, we evaluated the effects of a sustained increase in intracellular Ca
2+
concentrations induced by a receptor-bypassed stimulation with ionomycin, a Ca
2+
ionophore, on the endocytosis and down-regulation of H
1
receptors in Chinese hamster ovary cells. All cellular and cell-surface H
1
receptors were detected by the binding of [
3
H]mepyramine to intact cells sensitive to the hydrophobic and hydrophilic H
1
receptor ligands, mepyramine and pirdonium, respectively. The pretreatment of cells with ionomycin markedly reduced the mepyramine- and pirdonium-sensitive binding sites of [
3
H]mepyramine, which were completely abrogated by the deprivation of extracellular Ca
2+
and partially by a
ubiquitin-activating enzyme
inhibitor (UBEI-41), but were not affected by inhibitors of calmodulin (W-7 or calmidazolium) and protein kinase C (chelerythrine or GF109203X). These ionomycin-induced changes were also not affected by inhibitors of receptor endocytosis via clathrin (hypertonic sucrose) and caveolae/lipid rafts (filipin or nystatin) or by inhibitors of lysosomes (E-64, leupeptin, chloroquine, or NH
4
Cl), proteasomes (lactacystin or MG-132), and a Ca
2+
-dependent non-lysosomal
cysteine protease
(calpain) (MDL28170). Since H
1
receptors were normally detected by confocal immunofluorescence microscopy with an antibody against H
1
receptors, even after the ionomycin treatment, H
1
receptors appeared to exist in a form to which [
3
H]mepyramine was unable to bind. These results suggest that H
1
receptors are apparently down-regulated by a sustained increase in intracellular Ca
2+
concentrations with no process of endocytosis and lysosomal/proteasomal degradation of receptors.
...
PMID:Ca
2+
-dependent down-regulation of human histamine H
1
receptors in Chinese hamster ovary cells. 2906 96
