Beta-adrenergic inhibition of Na-K-Cl cotransport in lymphocytes.
Lymphocytes contain a homogeneous population of beta 2-adrenoceptors. However, their physiological role in the regulation of lymphocyte function, especially early in the activation/proliferation process, remains unclear. To study the role of beta-adrenergic activation on the regulation of membrane transport, we examined 86Rb uptake in the Jurkat human lymphoma cell line. 86Rb uptake was predominantly accounted for by bumetanide-sensitive uptake (74 +/- 2% total 86Rb uptake) and ouabain-sensitive uptake (20 +/- 2%). Bumetanide potently inhibited 86Rb uptake (50% inhibitory concentration = 210 +/- 40 nM), and bumetanide-sensitive uptake was dependent on extracellular sodium and chloride, consistent with uptake via Na-K-Cl cotransport. The beta-adrenergic agonist isoproterenol (10 microM) mediated a 50 +/- 11% reduction in bumetanide-sensitive uptake without a significant alteration in ouabain-sensitive uptake. The effect of isoproterenol was potent (50% effective concentration = 4.42 +/- 1.70 nM), stereoselective, and was inhibited by the beta-adrenergic antagonist nadolol. The effect of isoproterenol was mimicked by permeant adenosine 3',5'-cyclic monophosphate analogues but not by pindolol. These data indicate that beta-adrenoceptor activation decreases 86Rb uptake in lymphocytes via inhibition of Na-K-Cl cotransport. Modulation of this transporter could be one mechanism by which beta-adrenergic agonists regulate lymphocyte function.
Feldman
R D
RD
Department of Medicine, University of Western Ontario, London, Canada.
D000262:Adenylyl Cyclases / Q000378:metabolism; D002034:Bumetanide / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D000242:Cyclic AMP / Q000031:analogs & derivatives; D006801:Humans; D006982:Hypertonic Solutions / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007552:Isotonic Solutions / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism*; D009248:Nadolol / Q000494:pharmacology; D010869:Pindolol / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012413:Rubidium / Q000493:pharmacokinetics; D028021:Sodium-Potassium-Chloride Symporters; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D006982:Hypertonic Solutions; D007552:Isotonic Solutions; D011943:Receptors, Adrenergic, beta; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; D009248:Nadolol; D010869:Pindolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D012413:Rubidium; D011188:Potassium