Sensitization by calyculin A of brain capillary endothelial cells to endothelin-1

Br J Pharmacol. 1995 Mar;114(5):1014-6. doi: 10.1111/j.1476-5381.1995.tb13306.x.

Abstract

1. Cultured brain capillary endothelial cells of the rat respond to endothelin-1 (ET-1) by an increased activity of the Na+,K+,2Cl-, cotransporter and a mobilization of intracellular Ca2+ stores. 2. Calyculin A (1-30 nM), but not okadaic acid, sensitizes up to 100 fold the Na+,K+,2Cl- cotransporter to the action of ET-1. 3. Calyculin A (30 nM) does not modify the binding properties of ET-1 to ETA receptors. 4. Calyculin A (30 nM) inhibits ET-1 induced intracellular Ca2+ mobilization. 5. It is concluded that inhibition of protein phosphatase 1 selectively modifies the repertoire of intracellular actions of ET-1 and favours actions that are unrelated to the phospholipase C signalling cascade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / drug effects*
  • Calcium / metabolism
  • Capillaries / cytology
  • Capillaries / drug effects
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Endothelin Receptor Antagonists
  • Endothelins / antagonists & inhibitors
  • Endothelins / pharmacology*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Marine Toxins
  • Oxazoles / pharmacology*
  • Peptides, Cyclic / pharmacology
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Protein Phosphatase 1
  • Rats
  • Receptors, Endothelin / drug effects
  • Rubidium Radioisotopes
  • Sodium-Potassium-Chloride Symporters
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Vasoconstrictor Agents / pharmacology*

Substances

  • Carrier Proteins
  • Endothelin Receptor Antagonists
  • Endothelins
  • Marine Toxins
  • Oxazoles
  • Peptides, Cyclic
  • Receptors, Endothelin
  • Rubidium Radioisotopes
  • Sodium-Potassium-Chloride Symporters
  • Vasoconstrictor Agents
  • calyculin A
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1
  • Sodium-Potassium-Exchanging ATPase
  • cyclo(Trp-Asp-Pro-Val-Leu)
  • Calcium