title: Cyclosporine induced alterations in vasopressin signalling in the glomerular mesangial cell.
abstract: Nephrotoxicity is the major limiting factor in the clinical use of cyclosporine A (CyA), which in its acute form results in a decrease in renal blood flow and glomerular filtration rate. Contractile mesangial cells regulate glomerular capillary patency in response to vasoactive stimuli including vasopressin. Hence the effects of CyA on the cellular signalling mechanism of vasopressin in cultured glomerular mesangial cells were investigated. Vasopressin induced a transient rise in intracellular calcium which was enhanced in the presence of CyA. In addition, CyA decreased both basal and vasopressin stimulated PGE2 production. This inhibition was mediated at least in part at the level of arachidonate release and may involve inhibition of phospholipase A2. We conclude that the increased renal and systemic vasoconstriction that occurs with CyA treatment may be the result of an exaggerated rise in intracellular calcium combined with diminished production of vasorelaxant prostaglandins in response to vasoconstrictor hormones.
authors.affiliation: Department of Medicine, Toronto General Hospital, Ontario.
authors.forename: S
authors.initials: S
authors.lastname: Kremer
authors.forename: B
authors.initials: B
authors.lastname: Margolis
authors.forename: P
authors.initials: P
authors.lastname: Harper
authors.forename: K
authors.initials: K
authors.lastname: Skorecki
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D011458:Prostaglandins E / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D003524:Cyclosporins; D011458:Prostaglandins E; D014667:Vasopressins; D002118:Calcium