Increase in membrane fluidity modulates sodium-coupled uptakes and cyclic AMP synthesis by renal proximal tubular cells in primary culture.
In order to evaluate the influence of membrane fluidization on three apical transport systems and on a basolateral enzyme, and to analyse the mechanisms involved, we studied, in cultured rabbit proximal tubular cells, the effect of increasing concentrations of the local anesthetic drug benzyl alcohol on Na(+)-dependent uptakes of phosphate (Pi), methyl alpha-D-glucopyranoside (MGP), and L-alanine, as well as on basal and stimulated cyclic AMP content. At 10 mM, benzyl alcohol increased the Vmax of Pi uptake by 31%, decreased that of MGP uptake by 24%, and did not affect alanine uptake. Km values were not affected. Benzyl alcohol, up to 40 mM, increased in a concentration-dependent manner basal, PTH-stimulated, and cholera toxin-stimulated, but not forskolin-stimulated cyclic AMP accumulation. In the presence of 40 mM benzyl alcohol, the magnitude of PTH-induced inhibition of Pi uptake was enhanced from 11% to 24%. It is concluded that: (i) fluidization of apical membranes affected differently Na+/Pi, Na+/MGP, and Na+/alanine cotransports, reflecting differences in the lipidic environments of these transport system; (ii) fluidization of basolateral membranes enhanced PTH-stimulated cyclic AMP generation through improved coupling between the receptor-GS complex and the catalytic subunit of adenylate cyclase; (iii) these variations may result in physiological and pathophysiological modulation of the renal handling of solutes and of the phosphaturic effect of PTH.
INSERM U 251, Faculté de Médecine Xavier-Bichat, Université Paris, France.
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Friedlander
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Le Grimellec
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Amiel
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001592:Benzyl Alcohols / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis / Q000096:biosynthesis*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D008560:Membrane Fluidity; D010281:Parathyroid Hormone / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*
D001592:Benzyl Alcohols; D010281:Parathyroid Hormone; D005576:Colforsin; D002772:Cholera Toxin; D012964:Sodium; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine