title: Mechanisms of HCO(-)(3) secretion in the rabbit connecting segment.
abstract: The connecting tubule (CNT) contains alpha-(H(+)-secreting) and beta-(HCO(-)(3)-secreting) intercalated cells and is therefore likely to contribute to acid-base homeostasis. To characterize the mechanisms of HCO(-)(3) transport in the rabbit CNT, in which there is little definitive data presently available, we microdissected the segments from the superficial cortical labyrinth, perfused them in vitro, measured net HCO(-)(3) transport (J(HCO(-)(3))) by microcalorimetry, and examined the effects of several experimental maneuvers. Mean +/- SE basal J(HCO(-)(3)) was -3.4 +/- 0.1 pmol. min(-1). mm(-1) (net HCO(-)(3) secretion), and transepithelial voltage was -13 +/- 1 mV (n = 47). Net HCO(-)(3) secretion was markedly inhibited by removal of luminal Cl(-) or application of basolateral H(+)-ATPase inhibitors (bafilomycin or concanamycin), maneuvers that inhibit beta-intercalated cell function. Net HCO(-)(3) secretion was not affected by inhibitors of alpha-intercalated cell function (basolateral Cl(-) removal, basolateral DIDS, or luminal H(+)-ATPase inhibitors). Net HCO(-)(3) secretion was stimulated by isoproterenol and inhibited by acetazolamide. These data indicate that 1) CNTs secrete HCO(-)(3) via an apical DIDS-insensitive Cl(-)/HCO(-)(3) exchanger, mediated by a basolateral bafilomycin- and concanamycin-sensitive H(+)-ATPase; 2) inhibition of cytosolic carbonic anhydrase decreases HCO(-)(3) secretion; and 3) stimulation of beta-adrenergic receptors increases HCO(-)(3) secretion. The failure to influence net HCO(-)(3) transport by inhibiting alpha-intercalated cell apical H(+)-ATPases or basolateral Cl(-)/HCO(-)(3) exchange suggests that the CNT has fewer functioning alpha-intercalated cells than the cortical collecting duct. These are the first studies to examine the rate and mechanisms of HCO(-)(3) secretion by the rabbit CNT; this is clearly an important segment in mediating acid-base homeostasis.
authors.affiliation: Department of Pediatrics, University of Rochester School of Medicine, Rochester, New York 14642, USA.
authors.forename: S
authors.initials: S
authors.lastname: Tsuruoka
authors.forename: G J
authors.initials: GJ
authors.lastname: Schwartz
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000008:administration & dosage / Q000494:pharmacology; D000086:Acetazolamide / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D002712:Chlorides / Q000502:physiology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D054328:Proton Pump Inhibitors; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D011817:Rabbits
chemical_list: D001639:Bicarbonates; D002257:Carbonic Anhydrase Inhibitors; D002712:Chlorides; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D006180:Proton-Translocating ATPases; D007545:Isoproterenol; D000086:Acetazolamide; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid