Endothelin inhibits vasopressin-stimulated water permeability in rat terminal inner medullary collecting duct.
AUTOR(ES)
Nadler, S P
RESUMO
Renal tubule solute and water transport is subject to regulation by numerous factors. To characterize direct effects of the recently discovered peptide endothelin (ET) on renal tubule transport, we determined signaling mechanisms for ET effects on vasopressin (AVP)-stimulated water permeability (PF) in rat terminal inner medullary collecting duct (IMCD) perfused in vitro. ET caused a rapid, dose-dependent, and reversible fall in AVP- but not cyclic AMP-stimulated PF, suggesting that its effect on PF is by inhibition of cyclic AMP accumulation. Indomethacin did not block ET actions, ruling out a role for prostaglandins in its effect. The protein kinase C (PKC) inhibitor calphostin, or pretreatment of perfused tubules with pertussis toxin, blocked ET-mediated inhibition of AVP-stimulated PF. ET caused a transient increase in intracellular calcium ([Ca2+]i) in perfused tubules, an effect unchanged in zero calcium bath or by PT pretreatment. ET effects on PF and [Ca2+]i desensitized rapidly. Inhibition of PF was transient and largely abolished by 20 min ET preexposure, and repeat exposure to ET did not alter [Ca2+]i. In contrast, PGE2-mediated inhibition of AVP-stimulated PF and increase of [Ca2+]i were sustained and unaltered by prior exposure of IMCD to ET. Thus desensitization to ET is homologous. We conclude that ET is a potent inhibitor of AVP-stimulated water permeability in rat terminal IMCD. Signaling pathways for its effects involve both an inhibitory guanine nucleotide-binding protein and phospholipase-mediated activation of PKC. Since ET is synthesized by IMCD cells, this peptide may be an important autocrine modulator of renal epithelial transport.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=443192Documentos Relacionados
- Atrial natriuretic factor inhibits vasopressin-stimulated osmotic water permeability in rat inner medullary collecting duct.
- Vasopressin-stimulated phosphoinositide hydrolysis in cultured rat inner medullary collecting duct cells is mediated by the oxytocin receptor.
- Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct.
- Osmolar regulation of endothelin-1 production by rat inner medullary collecting duct.
- Anti sense DNA down-regulates proteins kinase C-epsilon and enhances vasopressin-stimulated Na+ absorption in rabbit cortical collecting duct.