|Budget Amount *help
¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1998 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1997 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1996 : ¥800,000 (Direct Cost : ¥800,000)
Dopamine (DA) causes natriuresis. Cortical collecting duct (COD) has been suggested to be a site responsible for this action. Previous studies reported the existence of either Di-like or D2-like receptor in the CCD and there is a controversy regarding the receptor subtype mediating in the dopanilne action in the collecting duct.
To approach this ciuestion, the subtype of dopamine receptors was characterized by using in vitro microperfusion technique, measuring transepithelial voltage (Vt, mV). In the rabbit, 1 nM to 10 muM basolateral DA induced a dose dependent depolarization of Vt.Pretreatment with domperidone, a selective D2-like receptor antagonist, abolished DA depolarization. In contrast, SCH23390, a selective Di-like receptor antagonist, failed to block the DA-induced Vt change. Furthermore, while SKF81297, a selective D1-hke receptor agonist, did not significantly depolarized Vt, bromocriptine, a selective D2-like receptor agonist, caused significant Vt change in a dose dependen
t manner. 10 to 100 muM luminal DA also depolarized Vt significantly. Pre-treatment of luminal SCH23390 completely blocked the luminal DA induced depolarization. In contrast1 luminal domperidone failed to suppress the luminal DA induced depolarization. Further luminal SKF81297 mimicked the effect of luminal DA, while luminal bromocriptine had no significant effect. Thus, DA receptors reside on both sides of the CCD epithelium but the receptor subtypes are distinct : basolaterally DA-2 like receptors and lurninally DA-1 like receptors. In terms of the natriuretic action of DA, basolateral DA was thought to play a major role, since basolateral DA-induced depolarization was blocked by basolateral ouabain or luminal amiloride, and lumen-to-bath 22Na flux was indeed suppressed by basolateral DA.On the other hand, the participation of luminal DA receptor was questionable since it was less sensitive to DA (require 10muM DA for significant depolarization) and the depolarization itself was also smaller than that induced by basolateral DA. Less