AJP - Cell Physiology, Vol 263, Issue 5 C1015-C1020, Copyright © 1992 by American Physiological Society
Beta-adrenergic inhibition of Na-K-Cl cotransport in lymphocytes
R. D. Feldman
Department of Medicine, University of Western Ontario, London, Canada.
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.
