TY - JOUR
T1 - Role of PGE2 in α2-induced inhibition of AVP- and cAMP-stimulated H2O, NA+, and urea transport in rat IMCD
AU - Rouch, Alexander J.
AU - Kudo, Lúcia H.
PY - 2000
Y1 - 2000
N2 - PGE2 inhibits osmotic water permeability (P(f)) in the rat inner medullary collecting duct (IMCD) via cellular events occurring after the stimulation of cAMP, i.e., post-cAMP-dependent events. The α2-agonists also inhibit P(f) in the rat IMCD via post-cAMP-dependent events. The purpose of this study was to determine whether PGE2 plays a role in α2-mediated inhibition of P(f), Na+, and urea transport in the rat IMCD. Isolated terminal IMCDs from Wistar rats were perfused to measure, in separate experiments, P(f), lumen-to-bath 22Na+ transport (J(lb)), and urea permeability (P(u)). Transport was stimulated with 220 pM arginine vasopressin (AVP) or 0.1 mM 8-(4-chlorophenylthio)-cAMP (CPT-cAMP). Indomethacin was used to inhibit endogenous prostaglandin synthesis, and the α2-agonists clonidine, oxymetazoline, and dexmedetomidine were used to test the role of PGE2 in the α2-mediated mechanism that inhibits transport. All agents were added to the bath. Indomethacin at 5 μM significantly elevated CPT-cAMP-stimulated P(f), J(lb), and P(u), and subsequent addition of 100 nM PGE2 reduced these transport parameters. Indomethacin reversed α2 inhibition of CPT-cAMP-stimulated P(f), J(lb), and P(u), and subsequent addition of PGE2 reduced transport in each case. Indomethacin partially reversed α2 inhibition of AVP-stimulated P(f), J(lb), and P(u), and PGE2 reduced transport back to the α2-inhibited level. These results indicate that PGE2 is a second messenger involved in the mechanism of transport inhibition mediated by α2-adrenoceptors via post-cAMP-dependent events in the rat IMCD.
AB - PGE2 inhibits osmotic water permeability (P(f)) in the rat inner medullary collecting duct (IMCD) via cellular events occurring after the stimulation of cAMP, i.e., post-cAMP-dependent events. The α2-agonists also inhibit P(f) in the rat IMCD via post-cAMP-dependent events. The purpose of this study was to determine whether PGE2 plays a role in α2-mediated inhibition of P(f), Na+, and urea transport in the rat IMCD. Isolated terminal IMCDs from Wistar rats were perfused to measure, in separate experiments, P(f), lumen-to-bath 22Na+ transport (J(lb)), and urea permeability (P(u)). Transport was stimulated with 220 pM arginine vasopressin (AVP) or 0.1 mM 8-(4-chlorophenylthio)-cAMP (CPT-cAMP). Indomethacin was used to inhibit endogenous prostaglandin synthesis, and the α2-agonists clonidine, oxymetazoline, and dexmedetomidine were used to test the role of PGE2 in the α2-mediated mechanism that inhibits transport. All agents were added to the bath. Indomethacin at 5 μM significantly elevated CPT-cAMP-stimulated P(f), J(lb), and P(u), and subsequent addition of 100 nM PGE2 reduced these transport parameters. Indomethacin reversed α2 inhibition of CPT-cAMP-stimulated P(f), J(lb), and P(u), and subsequent addition of PGE2 reduced transport in each case. Indomethacin partially reversed α2 inhibition of AVP-stimulated P(f), J(lb), and P(u), and PGE2 reduced transport back to the α2-inhibited level. These results indicate that PGE2 is a second messenger involved in the mechanism of transport inhibition mediated by α2-adrenoceptors via post-cAMP-dependent events in the rat IMCD.
KW - Inner medullary collecting duct
KW - Osmotic water permeability
KW - Second messengers
KW - Signaling pathways
KW - α-adrenoceptor
UR - http://www.scopus.com/inward/record.url?scp=0033840733&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.2000.279.2.f294
DO - 10.1152/ajprenal.2000.279.2.f294
M3 - Article
C2 - 10919849
AN - SCOPUS:0033840733
SN - 0002-9513
VL - 279
SP - F294-F301
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
IS - 2 48-2
ER -