Dual actions of vasopressin and oxytocin in regulation of water permeability in terminal collecting duct.
We conducted studies in isolated perfused terminal inner medullary collecting ducts (IMCD) from rats to investigate the roles of oxytocin and vasopressin in the regulation of osmotic water permeability. Vasopressin and oxytocin were found to have both stimulatory effects (at 0.1 nM) and inhibitory effects (at 10 nM) on osmotic water permeability. Measurements of adenosine 3',5'-cyclic monophosphate (cAMP) production demonstrated that both vasopressin and oxytocin increase cAMP production. Both the selective oxytocin-receptor agonist [Thr4,Gly7]oxytocin (10 nM) and the selective V1b agonist [deamino1,D-3-(pyridyl)Ala2,Arg8]vasopressin (10 nM) inhibited vasopressin-stimulated osmotic water permeability. In contrast, the selective V1a vasopressin-receptor agonist [Phe2,Ile3,Orn8]vasopressin (10 nM) had no effect on vasopressin-stimulated osmotic water permeability. These effects on water permeability correlated with the ability of the agents to transiently increase intracellular free calcium. The oxytocin/vasopressin-receptor antagonist [des-glycinamide9,d(CH2)5(1),O-Me-Tyr2,Thr4,Orn8]vasot ocin, which almost completely blocks vasopressin-induced calcium mobilization, also blocked the ability of 10 nM vasopressin to inhibit osmotic water permeability relative to that found with 0.1 nM vasopressin. We conclude the following. 1) Oxytocin, like vasopressin, has dual effects on osmotic water permeability, increasing it at subnanomolar concentrations and inhibiting it at suprananomolar concentrations. 2) Oxytocin, like vasopressin, can increase cAMP production, perhaps accounting for the increase in water permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
J S
JS
Han
Y
Y
Maeda
M A
MA
Knepper
D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D066298:In Vitro Techniques; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D009951:Ornipressin / Q000031:analogs & derivatives*; D009995:Osmosis; D010121:Oxytocin / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin / Q000502:physiology; D014667:Vasopressins / Q000494:pharmacology*; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology; D014867:Water / Q000378:metabolism*
D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; C082351:vasopressin, Phe(2)-Ile(3)-Orn(8)-; C082352:vasotocin, d(CH2)5-O-methyl-Tyr(2)-Thr(4)-Orn(8)-des-Gly-NH2(9)-; D014867:Water; D014667:Vasopressins; D009951:Ornipressin; D010121:Oxytocin; D000242:Cyclic AMP; D014668:Vasotocin