| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
1. Effect of oxytocin (OT) in the rabbit cortical collecting duct
Basolateral OT mimiced the effect of vasopressin V2 recetpor on transepithelial voltage (Vt) and osmotic permeeability in the rabbit CCD. However, these were considered to be mediated via basolateral V2 receptor but not OT receptor, since a specific OT agonist failed to reproduce these effects and V1 antagonist was unable to suppress these reactions.
2. Screening of tubular effect of OT by using several second messenger analonues.
1) cyclic GMP system : In cortical and medullary thick ascending limb (CAL and MAL, respectively), CCD, outer medullary and innner collecting duct (OMCD and IMCD, respectively) of the rabbit, uroguanylin had no effecton Vt.8-bromo-cGMP was inert in MAL as well. Though 8-Br-cGMP mimiced the effect of V2 receptor on Vt and water transport in the CCD, it appeared to be the cross-reaction to activate cAMP system instead of specific cGMP-mediated event.
2) intracellular Ca++ and protein kinase C (PKC) systems : The Ca-ionophore ionomycin stimulated Cl transport in rat MAL while suppresssed JCl in mouse MAL. PKC did not alter JCl in MAL of both species. Indomethacin pretreatment mitigated the ionomycin-induced suppression of JCl in the mouse, while the elevation of JCl in rat MAL was not changed. In mouse MAL, thus, elevation of intracellular Ca++ was thought to be inhibitory to Cl transport in mouse MAL and this effect is, in part, prostaglandin dependent. On the other hand, elevation of intracellular Ca++ may employ distinct signalling network system in enhancing JCl in rat MAL.
3. Summary
These exploration implies that OT receptor is unlikely to be a n important mediator of vasopressin action in the collectong duct. However, it is to be evatulated further that, in MAL, OT receptor, if any, may mediate the vasopressin actions via intracellular Ca++ system in a species-dependent manner.
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