cAMP-dependent control of Na+/H+ antiport by AVP, PTH, and PGE2 in rat medullary thick ascending limb cells.
Antidiuretic hormone and parathyroid hormone (PTH) inhibit HCO3- absorption by the rat medullary thick ascending limb (MTAL). Studies were performed on rat MTAL tubule suspension to specify the H(+)-HCO3- membrane transporters affected by these hormones and the implicated intracellular second messengers. Arginine vasopressin (AVP) and PTH stimulated cell adenosine 3',5'-cyclic monophosphate (cAMP) production with a relative rank order potency of AVP > rat PTH-(1-34) > bovine PTH-(1-84). Significant cell acidification in HCO3- -CO2-free medium, monitored in 2'7'-bis(carboxyethyl)-5(6')-carboxyfluorescein-loaded cells, was caused by 0.1 nM AVP, 1 nM rat PTH-(1-34), but not by < 100 nM bovine PTH-(1-84), as well as by 10(-4) M 8-bromo-cAMP and 2 x 10(-5) M forskolin; 10 nM AVP or rat PTH-(1-34) did not alter the intracellular pH when Na+/H+ antiport was inhibited by 2 mM amiloride. Prostaglandin E2 (PGE2, 10(-6) M), which inhibited AVP-stimulated cell cAMP production, reduced by 35% the cell acidification response to 10 nM AVP. AVP and 8-bromo-cAMP inhibited Na+/H+ antiport-dependent cell pH recovery from intracellular acidification, which was explained by a decrease in the Vmax of the antiporter. AVP did not directly affect K(+)-HCO3- cotransport and plasma membrane H(+)-ATPase of rat MTAL cells. Cytosolic calcium ([Ca2+]i), monitored in fura-2-loaded cells, was unaffected by up to 1 nM AVP, 100 nM PTH, glucagon, calcitonin, and oxytocin, and 1 microM PGE2; however, 100 nM AVP, but not 1-desamino-8-D-AVP (dDAVP), caused a peak increase in [Ca2+]i, even in the absence of extracellular Ca2+, and stimulated cell accumulation of [3H]inositol phosphates.(ABSTRACT TRUNCATED AT 250 WORDS)
Physiologie et Endocrinologie Cellulaire Rénale, Institut National de la Santé et de la Recherche Médicale, Unité 356, Université Pierre et Marie Curie, Paris, France.
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Borensztein
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Juvin
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Vernimmen
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Poggioli
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Paillard
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Bichara
D000818:Animals; D001127:Arginine Vasopressin / Q000502:physiology*; D001639:Bicarbonates / Q000378:metabolism; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D015232:Dinoprostone / Q000502:physiology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007679:Kidney Medulla; D008138:Loop of Henle / Q000502:physiology*; D008297:Male; D010281:Parathyroid Hormone / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers
D001639:Bicarbonates; D002352:Carrier Proteins; D007295:Inositol Phosphates; D010281:Parathyroid Hormone; D017923:Sodium-Hydrogen Exchangers; D001127:Arginine Vasopressin; D000242:Cyclic AMP; D015232:Dinoprostone; D002118:Calcium