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:2.3.1.21 (
CPT
)
4,580
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
1.
Phenylarsine oxide
(
PAO
) is commonly used to inhibit tyrosine phosphatase activity. However,
PAO
can affect a variety of different processes because of its ability to promote sulfhydryl oxidation. In the present study, we investigated the effects that
PAO
has on basal and beta-adrenergically stimulated L-type Ca(2+) channel activity in isolated cardiac myocytes. 2. Extracellular application of
PAO
transiently stimulated the basal L-type Ca(2+) channel activity, whereas it irreversibly inhibited protein kinase A (PKA)-dependent regulation of channel activity by isoproterenol, forskolin and 8-
CPT
-cAMP (8-p-chlorophenylthioadenosine 3',5'-cyclic monophosphate).
PAO
also inhibited channel activity irreversibly stimulated in the presence of adenosine 5'-(3-thiotriphosphate) tetralithium salt. 3. Neither the stimulatory nor the inhibitory effects of
PAO
were affected by the tyrosine kinase inhibitor lavendustin A, suggesting that tyrosine phosphorylation is not involved. 4. Extracellular application of the sulfhydryl-reducing agent dithiothreitol (DTT) antagonized both the stimulatory and inhibitory effects of
PAO
. Yet, following intracellular dialysis with DTT, only the inhibitory effect of
PAO
was antagonized. 5. The inhibitory effect of
PAO
was mimicked by intracellular, but not extracellular application of the membrane impermeant thiol oxidant 5,5'-dithio-bis(2-nitrobenzoic acid). 6. These results suggest that the stimulatory effect of
PAO
results from oxidation of sulfhydryl residues at an extracellular site and the inhibitory effect is due to redox regulation of an intracellular site that affects the response of the channel to PKA-dependent phosphorylation. It is concluded that the redox state of the cell may play a critical role in modulating beta-adrenergic responsiveness of the L-type Ca(2+) channel in cardiac myocytes.
...
PMID:Redox modulation of basal and beta-adrenergically stimulated cardiac L-type Ca(2+) channel activity by phenylarsine oxide. 1517 60
