Beta-adrenergic regulation of Cl- and HCO3- secretion by Clara cells.
Previous studies on beta-adrenergic agonist regulation of ion transport in distal airways yielded discordant results. The present study was performed to further investigate this process in isolated bronchiolar epithelial cells and resolve the discrepancies. Epithelial enriched in rabbit nonciliated bronchiolar epithelial (Clara) cells responded to isoproterenol with a biphasic increase in transepithelial short circuit current (Isc) and decrease in transepithelial resistance (Rt). The first phase of the Isc response consisted of a transient, 11 microA/cm2 increase in current that was inhibited by HCO3(-)-free bathing solutions, but was not inhibited by amiloride, bumetanide, or Cl(-)-free bathing solutions. The ED50 for isoproterenol stimulation of the initial peak was 81 pM. The second phase was a prolonged, 27 microA/cm2 elevation in Isc. Amiloride in the apical bath inhibited basal Isc and the prolonged change in Isc induced by isoproterenol. Bumetanide in the basolateral bath and bilateral Cl(-)-free bathing solutions likewise inhibited the plateau phase of the isoproterenol response, and the inhibition was accentuated in the presence of amiloride. HCO3(-)-free bathing solutions did not inhibit the plateau phase. The ED50 for isoproterenol stimulation of the plateau phase was 6.3 nM. The bioelectric response to isoproterenol was mimicked by isobutylmethylxanthine (IBMX) and, to a lesser degree, by dibutyryl-cAMP. Culturing the cells in medium containing cholera toxin completely inhibited the bioelectric response, yet the preparations continued to respond to isoproterenol with an increase in cAMP production. These results indicated that beta-adrenergic stimulation of Clara cells induced electrogenic transepithelial secretion of Cl- and HCO3- and resolved discrepancies between previous studies.
Van Scott
M R
MR
Department of Physiology, East Carolina University, Greenville, North Carolina, USA.
Penland
C M
CM
Welch
C A
CA
Lazarowski
E
E
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001980:Bronchi / Q000502:physiology*; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D004594:Electrophysiology; D004848:Epithelium / Q000502:physiology; D017136:Ion Transport / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001639:Bicarbonates; D002712:Chlorides; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol