AJP - Cell Physiology, Vol 264, Issue 3 C568-C576, Copyright © 1993 by American Physiological Society
Alpha 2-adrenergic, but not imidazole, agonists activate NaCl cotransport in rabbit tracheal epithelial cells
C. M. Liedtke, J. Furin and P. Ernsberger
Department of Pediatrics, Rainbow Babies and Children Hospital, Cleveland, Ohio.
The adrenergic agonist clonidine activates NaCl cotransport in rabbit
tracheocytes. With the use of the high-affinity analogue
p-[125I]iodoclonidine, binding of clonidine to cells was determined to fit
a two-site model, with one site of high specificity for alpha 2-adrenergic
(alpha 2-AR) and the other with a high affinity for I1-imidazol(in)e (I1)
receptors. Total density of binding sites for both receptors was similar at
18 fmol/mg protein. Moxonidine displayed a 166-fold greater specificity for
I1 receptors compared with cimetidine. Bumetanide-sensitive Na or Cl
transport was stimulated by the alpha 2-AR agonists clonidine or guanabenz
but not by the I1 agents cimetidine or moxonidine. I1 agonists-stimulated
Na transport was detected only in the presence of bumetanide. Prazosin did
not block clonidine-stimulated NaCl uptake or efflux, indicating the
presence of an alpha 2A-AR subtype. Addition of clonidine either before or
after incubation with l-isoproterenol or forskolin did not attenuate the
time- and dose-dependent increase in adenosine 3',5'-cyclic monophosphate
(cAMP) levels. Thus clonidine stimulates NaCl cotransport in rabbit
tracheocytes through an alpha 2A-AR mechanism that does not require cAMP
for signal transduction. In addition, I1-imidazol(in)e receptors stimulate
Na transport in rabbit tracheocytes through an unidentified pathway.
