Hormonal regulation of proton secretion in rabbit medullary collecting duct.

Abstract

With the exception of aldosterone, little is known about the hormonal regulation of distal nephron acidification. These experiments investigated the effects of prostaglandin E2, indomethacin, lysyl-bradykinin, 8-bromo-cyclic AMP, and forskolin on proton secretion in the major acidifying segment of the distal nephron, the medullary collecting duct from inner stripe of outer medulla.Using in vitro microperfusion and microcalorimetry, net bicarbonate reabsorption (proton secretion) was measured in rabbit medullary collecting ducts before, during, and after exposure to each test substance. PGE2 reduced proton secretion 12.2%, while the following substances stimulated proton secretion: indomethacin 14.2%; 8-bromo-cyclic AMP 34.5%; forskolin 39%. Lysylbradykinin was without effect.These studies demonstrate that distal nephron acidification, in addition to being stimulated by aldosterone, is significantly inhibited by the hormone PGE2. The stimulation of proton secretion by cAMP suggests that other hormones known to activate adenylate cyclase may also influence distal nephron acidification.

Mineralocorticoid modulation of apical and basolateral membrane H+/OH-/HCO3- transport processes in the rabbit inner stripe of outer medullary collecting duct.

“…In addition, our ADX results are of a similar magnitude to the 40% reduction in net transepithelial HCO-absorption we found previously (8). Of note, the measured H' flux (JH) across the apical membrane in our studies was less than rates of net transepithelial H+ secretion found in control and DOCA tubules perfused in vitro (3,8). The difference may be a result ofthe nominal presence of ambient CO2/ HCO in our studies that was removed to decrease any contribution to pHi by the Cl/HCO-exchanger (9).…”

“…The DOCA results are of a similar magnitude to the increase in net transepithelial HCO-absorption found by Stone et al (3) in OMCDj's dissected from rabbits chronically treated with DOCA. In addition, our ADX results are of a similar magnitude to the 40% reduction in net transepithelial HCO-absorption we found previously (8). Of note, the measured H' flux (JH) across the apical membrane in our studies was less than rates of net transepithelial H+ secretion found in control and DOCA tubules perfused in vitro (3,8).…”

“…The technique ofin vitro microperfusion ofisolated rabbit OMCDj was used as previously described (8). Briefly, female New Zealand White rabbits weighing 1.5-2.0 kg were maintained on standard laboratory chow and tap water ad lib.…”

Effects of protein kinase C activation on sodium, potassium, chloride, and total CO2 transport in the rabbit cortical collecting tubule.

“…CCT were dissected and perfused in vitro as previously described (10,11). Briefly, female New Zealand White rabbits weighing 1.5-2.5 kg were maintained on standard laboratory chow and tap water ad lib.…”

PKA Regulates Vacuolar H+-ATPase Localization and Activity via Direct Phosphorylation of the A Subunit in Kidney Cells

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Acid secretion in epithelial cells is actively regulated by environmental signals, although the mechanisms by which these cues are translated into activation of H ϩ transport pathways remains the subject of intense research (11,(15)(16)(17)(18)(19). For example, the V-ATPase is regulated by several pathways, which involve CO 2 , phosphatidylinositol 3-kinase, aldolase, phosphofructokinase, actin, microtubules, and angiotensin in a variety of mammalian cellular systems (20 -27).

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