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Platelet activating factor inhibits Cl and K transport in the medullary thick ascending limb
C Bailly1, C Barlet-Bas, C Amiel
1Laboratoire de Physiologie Rénale, Faculté Xavier Bichat, Université Paris 7, INSERM U.251, France.
Abstract:
Since the kidney medulla was reported to generate platelet activating factor (PAF), we investigated a possible effect of this agent on the reabsorptive function of in vitro microperfused medullary thick ascending limbs from mouse kidney (mTAL). PAF, 10(-7) M in the bath, significantly decreased the net chloride flux (JCl) from 48.8 +/- 7.1 to 27.4 +/- 5.7 pmol/min. This effect was reversible, blocked by the antagonist BN 50730, and not reproduced by the inactive metabolite lyso-PAF. PAF inhibited the transepithelial potential difference with a threshold at 10(-9) M. In the presence of isoproterenol, the PAF-induced decrease of JCl was not significantly different from that observed in basal conditions; moreover, PAF did not modify the adenylate cyclase activity in isolated mTALs, either in basal condition or under stimulation by isoproterenol. The effect of PAF on JCl was not prevented by mepacrine, NDGA associated with proadifen, or adenosine desaminase. When the apical Na-K-2Cl cotransport was blocked by furosemide or bumetanide, a net K secretion occurred (-1.1 +/- 0.2 pmol/min), which was significantly decreased by PAF (-0.06 +/- 0.3 pmol/min). Moreover, it was verified on isolated mTALs that PAF did not modify the Na,K-ATPase activity. It is concluded that PAF inhibits the reabsorptive function of the mTAL, as indicated by the decrease of Cl reabsorption and K secretion. This effect could not be accounted for by adenosine or arachidonic acid metabolite action, and was not mediated by an inhibition of the adenylate cyclase activity.
Insights
Platelet-activating factor (PAF) was found to inhibit kidney function by decreasing chloride reabsorption and potassium secretion in the medullary thick ascending limb. This effect was specific to PAF and not mediated by other signaling pathways.
Area of Science:
- Nephrology
- Renal Physiology
- Molecular Pharmacology
Background:
- The kidney medulla is known to produce platelet-activating factor (PAF).
- The functional role of PAF in kidney reabsorptive processes remains largely unexplored.
- Understanding PAF's effects is crucial for comprehending renal salt and water balance.
Purpose of the Study:
- To investigate the impact of platelet-activating factor (PAF) on the reabsorptive function of the medullary thick ascending limb (mTAL) of the mouse kidney.
- To elucidate the specific transport mechanisms affected by PAF in the mTAL.
- To determine the signaling pathways involved in PAF's action within the mTAL.
Main Methods:
- In vitro microperfusion of isolated mouse kidney medullary thick ascending limbs (mTAL).
- Measurement of net chloride flux (JCl) and transepithelial potential difference.
- Assessment of potassium secretion and Na,K-ATPase activity.
- Pharmacological inhibition studies using PAF antagonists, isoproterenol, and inhibitors of specific transport pathways.
Main Results:
- Platelet-activating factor (PAF) significantly decreased net chloride flux (JCl) in mTALs.
- PAF inhibited the transepithelial potential difference in a dose-dependent manner.
- PAF reduced net potassium secretion when Na-K-2Cl cotransport was blocked, and did not affect Na,K-ATPase activity.
Conclusions:
- Platelet-activating factor (PAF) inhibits the reabsorptive function of the medullary thick ascending limb (mTAL).
- PAF's inhibitory effect is characterized by reduced chloride reabsorption and potassium secretion.
- The observed effects are specific to PAF and not mediated by adenosine, arachidonic acid metabolites, or adenylate cyclase inhibition.