Alpha 2-adrenergic, but not imidazole, agonists activate NaCl cotransport in rabbit tracheal epithelial cells.
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.
Liedtke
C M
CM
Department of Pediatrics, Rainbow Babies and Children Hospital, Cleveland, Ohio.
Furin
J
J
Ernsberger
P
P
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D027963:Chloride-Bicarbonate Antiporters; D003000:Clonidine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D004347:Drug Interactions; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology / Q000648:ultrastructure; D006143:Guanabenz / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors; D007457:Iodine Radioisotopes; D007545:Isoproterenol / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000187:drug effects / Q000502:physiology; D011955:Receptors, Drug / Q000187:drug effects / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D049992:Sodium Chloride Symporters; D027981:Symporters; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014132:Trachea / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D007093:Imidazoles; D054755:Imidazoline Receptors; D007457:Iodine Radioisotopes; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; D049992:Sodium Chloride Symporters; D027981:Symporters; D005576:Colforsin; C029899:imidazole; C043482:moxonidine; D000242:Cyclic AMP; D013930:Thromboxane-A Synthase; D006143:Guanabenz; D007545:Isoproterenol; D003000:Clonidine; D011224:Prazosin