Epinephrine and norepinephrine enhance p-aminohippurate transport into basolateral membrane vesicles.
The effect of exogenous l-norepinephrine (NE) and l-epinephrine (EP) on transmembrane transport of p-aminohippurate (PAH) was studied in rat proximal tubular basolateral membrane vesicles. A gradient of 50 mM Na+ (out greater than in) and preloading of vesicles with unlabeled PAH were utilized to promote the influx of [3H]PAH into the vesicles. At final concentrations of 1 microM, NE and EP each produced significant elevations in vesicle uptake of [3H]PAH. The enhancement of PAH transport by NE or EP was inhibited by either phentolamine (100 microM) or yohimbine (100 microM). Prazosin (100 microM) or atenolol (100 microM) were unable to inhibit the response to NE. Similarly, prazosin or propranolol (100 microM) were unable to inhibit the response to EP. Clonidine (1 microM) also produced a significant elevation of PAH uptake, an effect inhibited by both phentolamine and yohimbine. Basolateral Na+-K+-adenosine triphosphatase activity also was increased significantly by either NE or EP (1 microM). Both agonists produced significant elevations of PAH uptake into vesicles preloaded with ATP. However, in the absence of NE or EP, PAH uptake into ATP-loaded vesicles was not significantly greater than into control vesicles. It was concluded that NE and EP enhance Na+-coupled PAH transport and that this effect may be mediated by alpha-2 adrenergic receptors. Activation of Na+-K+-adenosine triphosphatase is a possible mechanism whereby adrenergic agonists may exert effects on Na+-coupled transport across the basolateral membrane.
Jensen
R E
RE
Department of Pharmacology, University of Nebraska College of Medicine, Omaha.
Berndt
W O
WO
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000618:Aminohippuric Acids / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000032:analysis / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics*
D000618:Aminohippuric Acids; D014638:Vanadates; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D009638:Norepinephrine; D010130:p-Aminohippuric Acid; D004837:Epinephrine