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Inhibition of the Kir6.1/SUR2B channel by arginine vasopressin via V1a receptor and protein kinase C
Author(s) -
SHI WEIWEI,
Cui Ningren,
Shi Yun,
Zhang Xiaoli,
Yang Yang,
Liu Yuan,
Jiang Chun
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a875-b
Subject(s) - pinacidil , calphostin c , vasopressin , protein kinase c , vasoconstriction , vasopressin receptor , chemistry , chelerythrine , receptor , arginine , arginine vasopressin receptor 2 , medicine , endocrinology , glibenclamide , pharmacology , phosphorylation , biochemistry , biology , antagonist , amino acid , diabetes mellitus
Kir6.1/SUR2B channel is the major isoform of KATP channels in vascular smooth muscles. Genetic disruption of either subunit causes vascular dysfunctions. To demonstrate Kir6.1/SUR2B channel as a target of vasopressin (AVP), we performed the studies on the Kir6.1/SUR2B channel and isolated rat mesenteric arterial rings. In HEK cells transfected with Kir6.1, SUR2B and V1a receptor, whole‐cell currents were activated by pinacidil and inhibited by glibenclamide. AVP exposure produced a concentration‐dependent inhibition of the pinacidil‐activated currents. The current inhibition was mediated by a suppression of Po with little effect on unitary conductance. PMA, a selective PKC activator, strongly inhibited the pinacidil‐activated currents, and abolished the effect of AVP. Such an effect was not seen with 4alpha‐PDD. The effect of AVP was significantly diminished by calphostin‐C and a PKC inhibitory peptide. In isolated mesenteric artery rings, AVP also produced concentration‐dependent vasoconstrictions with EC50 6.5nM. At the maximum effect, pinacidil relaxed the vasoconstriction completely. The magnitude of the AVP‐induced vasoconstriction was significantly reduced with calphostin‐C. These results thus indicate that the Kir6.1/SUR2B channel is a target molecule of AVP, and the channel inhibition relied on Gq coupled V1a receptor and PKC.