title: Apical location and inhibition by arginine vasopressin of K+/H+ antiport of the medullary thick ascending limb of rat kidney.
abstract: To characterize and localize a K+/H+ antiport mechanism in the renal medullary thick ascending limb (MTAL), membrane vesicles were isolated from a rat MTAL homogenate. K+/H+ antiport (in > out H+ gradient-stimulated 86Rb+ uptake) was abolished by barium and verapamil (apparent Ki of 55 microM) but unaffected by other K+ channel blockers such as quinidine and high amiloride concentrations. SCH 28080, a H+/K+-ATPase blocker, did not affect K+/H+ antiport. K+/H+ antiport activity was correlated positively with the enrichment factor of the membranes in the apical marker enzyme alkaline phosphatase (r = 0.875, p < 0.01) and negatively correlated with the enrichment factor in basolateral Na+/K+-ATPase (r = -0.665, p < 0.05). Moreover, a functional interaction occurred with Na+/H+ exchange (NHE) consistent with colocation of K+/H+ antiport and apical NHE-3, not basolateral NHE-1. K+/H+ antiport was shown by intracellular pH measurements to be inhibited by arginine vasopressin and 8-bromo-cAMP through cAMP-dependent protein kinase (protein kinase A) activation. These results demonstrate the presence of a K+/H+ antiport mechanism, which is inhibited by arginine vasopressin via protein kinase A, in the apical membrane of the MTAL.
authors.affiliation: Physiologie et Endocrinologie Cellulaire Rénale, INSERM U. 356, Université Pierre et Marie Curie and Hôpital Broussais, 75270 Paris, cédex 06, France.
authors.forename: A
authors.initials: A
authors.lastname: Attmane-Elakeb
authors.forename: H
authors.initials: H
authors.lastname: Boulanger
authors.forename: C
authors.initials: C
authors.lastname: Vernimmen
authors.forename: M
authors.initials: M
authors.lastname: Bichara
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D017920:Antiporters / Q000037:antagonists & inhibitors* / Q000187:drug effects; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001464:Barium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000494:pharmacology; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D027961:Potassium-Hydrogen Antiporters; D051381:Rats; D017207:Rats, Sprague-Dawley; D012076:Renal Agents / Q000494:pharmacology*; D012413:Rubidium / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
chemical_list: D017920:Antiporters; D002121:Calcium Channel Blockers; D004232:Diuretics; D004791:Enzyme Inhibitors; D007093:Imidazoles; D015221:Potassium Channels; D027961:Potassium-Hydrogen Antiporters; D012076:Renal Agents; C035235:Sch 28080; D001127:Arginine Vasopressin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D001464:Barium; D000584:Amiloride; D006859:Hydrogen; D014700:Verapamil; D017868:Cyclic AMP-Dependent Protein Kinases; D000251:Adenosine Triphosphatases; D012413:Rubidium