Involvement of phosphatidylcholine-specific phospholipase C in thromboxane A2 receptor-mediated extracellular Ca²âº influx in rat aorta.
Eur J Pharmacol
; 677(1-3): 123-30, 2012 Feb 29.
Article
en En
| MEDLINE
| ID: mdl-22200631
An involvement of signal transduction other than phosphatidylinositol turnover in thromboxane A(2) receptor (TP receptor)-mediated vascular contraction was investigated in rat aorta. The contraction induced by U46619, a TP receptor agonist, at low concentrations (≤ 30 nM) was partially inhibited by verapamil, an inhibitor of voltage-dependent Ca(2+) channels (VDCC), and was further diminished in Ca(2+)-free solution. Twenty nanomolar of U46619 induced contraction and elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)), which were consisted of two phases; slowly developing first phase followed by quickly rising second phase. The second phase was inhibited by verapamil, and all the [Ca(2+)](i) response was abolished in Ca(2+)-free solution. The contraction and [Ca(2+)](i) elevation induced by 20 nM U46619 were not inhibited by U73122, an inhibitor of phosphatidylinositol-specific phospholipase C, or GF109203X, a protein kinase C inhibitor, but were abolished by D609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC). However, D609 had no effect on those induced by 1 µM phenylephrine. The U46619-induced responses were also partially inhibited by cation channel blockers, 2-APB and LOE908. The inhibition by LOE908 was abolished in the presence of verapamil, suggesting that LOE908-sensitive cation channels lead to the activation of VDCC by depolarizing plasma membrane. In contrast, 2-APB further diminished the U46619-induced [Ca(2+)](i) elevation in the presence of verapamil. In conclusion, TP receptor stimulation is suggested to be coupled with PC-PLC. Diacylglycerol produced by PC-PLC seems to activate two types of cation channels independently of PKC, which in turn leads to VDCC-dependent and independent Ca(2+) influx, thereby eliciting contraction.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Aorta
/
Fosfatidilcolinas
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Fosfolipasas de Tipo C
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Calcio
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Receptores de Tromboxano A2 y Prostaglandina H2
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Espacio Extracelular
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Países Bajos