Stimulation of A(2a) adenosine receptor abolishes the inhibitory effect of arachidonic acid on the basolateral 50-pS K channel in the thick ascending limb.
Am J Physiol Renal Physiol
; 300(4): F906-13, 2011 Apr.
Article
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| MEDLINE
| ID: mdl-21209003
ABSTRACT
The basolateral 50-pS K channels are stimulated by a cAMP-dependent pathway and inhibited by cytochrome P-450-omega-hydroxylase-dependent metabolism of arachidonic acid (AA) in the rat thick ascending limb (TAL). We now used the patch-clamp technique to examine whether stimulation of adenosine A(2a) receptor modulates the inhibitory effect of AA on the basolateral 50-pS K channels in the medullary TAL. Stimulation of adenosine A(2a) receptor with CGS-21680 or inhibition of phospholipase A2 (PLA2) with AACOCF3 increased the 50-pS K channel activity in the TAL. Western blot demonstrated that application of CGS-21680 decreased the phosphorylation of PLA(2) at serine residue 505, an indication of inhibiting PLA2 activity. In the presence of CGS-21680, inhibition of PLA2 had no further effect on the basolateral 50-pS K channels. The possibility that CGS-21680-induced stimulation of the basolateral 50-pS K channels was partially achieved by inhibition of PLA2 in the TAL was also supported by the observation that CGS-21680 had no additional effect in the presence of AACOCF3. Moreover, stimulation of adenosine A(2a) receptor with CGS-21680 also abolished the inhibitory effect of AA and 20-hydroxyeicosatetraenoic acid (20-HETE) on the 50-pS K channels. The effect of CGS-21680 on AA and 20-HETE-mediated inhibition of the 50-pS K channels was mediated by cAMP because application of membrane-permeable cAMP analog, dibutyryl-cAMP, not only increased the 50-pS K channel activity but also abolished the inhibitory effect of AA and 20-HETE. We conclude that stimulation of adenosine A(2a) receptor increased the 50-pS K channel activity in the TAL, an effect that is achieved by suppression of PLA2 activity and 20-HETE-induced inhibition.
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1
Base de datos:
MEDLINE
Asunto principal:
Canales de Potasio
/
Ácido Araquidónico
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Receptor de Adenosina A2A
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Asa de la Nefrona
Idioma:
En
Revista:
Am J Physiol Renal Physiol
Asunto de la revista:
FISIOLOGIA
/
NEFROLOGIA
Año:
2011
Tipo del documento:
Article