Platelet activating factor inhibits Cl and K transport in the medullary thick ascending limb.
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.
Bailly
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Laboratoire de Physiologie Rénale, Faculté Xavier Bichat, Université Paris 7, INSERM U.251, France.
Barlet-Bas
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Amiel
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D000042:Absorption; D000818:Animals; D002712:Chlorides / Q000493:pharmacokinetics*; D004594:Electrophysiology; D007679:Kidney Medulla; D008138:Loop of Henle / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism / Q000493:pharmacokinetics*
D002712:Chlorides; D010972:Platelet Activating Factor; D011188:Potassium