Contractile regulation of the Na(+)-K(+)-2Cl(-) cotransporter in vascular smooth muscle.

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Akar F, Jiang G, Paul RJ, O'Neill WC

Contractile regulation of the Na(+)-K(+)-2Cl(-) cotransporter in vascular smooth muscle.

Am J Physiol Cell Physiol. 2001 Aug;281(2):C579-84.

PubMed ID

11443057 [ View in PubMed

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Abstract

Vasoconstrictors activate the Na(+)-K(+)-2Cl(-) cotransporter NKCC1 in rat aortic smooth muscle, but the mechanism is unknown. Efflux of (86)Rb(+) from rat aorta in response to phenylephrine (PE) was measured in the absence and presence of bumetanide, a specific inhibitor of NKCC1. Removal of extracellular Ca(2+) completely abolished the activation of NKCC1 by PE. This was not due to inhibition of Ca(2+)-dependent K(+) channels since blocking these channels with Ba(2+) in Ca(2+)-replete solution did not prevent activation of NKCC1 by PE. Stimulation of NKCC1 by PE was inhibited 70% by 75 microM ML-9, 97% by 2 microM wortmannin, and 70% by 2 mM 2,3-butanedione monoxime, each of which inhibited isometric force generation in aortic rings. Bumetanide-insensitive Rb(+) efflux, an indication of Ca(2+)-dependent K(+) channel activity, was reduced by ML-9 but not by the other inhibitors. Stretching of aortic rings on tubing to increase lumen diameter to 120% of normal almost completely blocked the stimulation of NKCC1 by PE without inhibiting the stimulation by hypertonic shrinkage. We conclude that activation of the Na(+)-K(+)-2Cl(-) cotransporter by PE is the direct result of smooth muscle contraction through Ca(2+)-dependent activation of myosin light chain kinase. This indicates that the Na(+)-K(+)-2Cl(-) cotransporter is regulated by the contractile state of vascular smooth muscle.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Bumetanide	Solute carrier family 12 member 2	Protein	Humans	Yes	Inhibitor	Details