Sodium-coupled organic anion transport by Cancer borealis urinary bladder.
Recently, p-aminohippurate (PAH) transport by rat renal basolateral membrane (BLM) vesicles was shown to be coupled indirectly to the Na+ gradient through PAH-glutarate exchange and Na(+)-glutarate cotransport. We have examined the mechanism of PAH transport in Cancer borealis urinary bladder, a simple flat-sheet epithelium that is functionally analogous to vertebrate renal proximal tubule. These experiments indicate that crab bladder is capable of both Na(+)-coupled glutarate uptake and PAH-glutarate exchange and that PAH uptake may be coupled to Na+ in the intact tissue. First, glutarate uptake by intact bladder was lithium sensitive, Na(+) dependent, and inhibited by other dicarboxylates. In flux chambers, the bladder exhibited net glutarate secretion and tissue accumulation occurred primarily from the basolateral side. Furthermore, both BLM and brush-border membrane (BBM) vesicles also exhibited lithium-sensitive Na(+)-coupled glutarate uptake. Second, imposition of an in greater than out glutarate gradient markedly stimulated PAH uptake by bladder BLM vesicles, demonstrating PAH-glutarate exchange. In contrast, exchange was absent in BBM vesicles. Third, in intact bladder tissue, external glutarate increased the steady-state tissue-to-medium ratio for PAH from 14 +/- 1 to 19 +/- 1.5. This increase was both lithium inhibitable and Na+ dependent. Thus not only do bladder BLM show all the elements needed for indirect coupling of PAH transport to the Na+ gradient, but indirect coupling to Na+ can also drive uphill PAH transport in the intact epithelium.
Smith
P M
PM
Laboratory of Cellular and Molecular Pharmacology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Miller
D S
DS
Pritchard
J B
JB
D000818:Animals; D000838:Anions / Q000378:metabolism / Q000493:pharmacokinetics*; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D003445:Crustacea / Q000378:metabolism*; D004594:Electrophysiology; D004848:Epithelium / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D005977:Glutarates / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D012727:Sex Characteristics; D012964:Sodium / Q000378:metabolism / Q000502:physiology*; D001743:Urinary Bladder / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D010130:p-Aminohippuric Acid / Q000378:metabolism / Q000493:pharmacokinetics
D000838:Anions; D005977:Glutarates; D012964:Sodium; D010130:p-Aminohippuric Acid