[Airway epithelial beta 3-adrenergic receptor--effect on bioelectric properties and its mechanism of action].
To characterize the "atypical" beta-adrenergic receptor (beta 3-adrenergic receptor) and its action on ion transport across airway mucosa, we measured the bioelectric properties of canine cultured tracheal epithelium under short-circuited conditions in vitro. Submucosal but mucosal addition of BRL37344, a selective beta 3-adrenergic agonist, increased short-circuit current (Isc) in a dose-dependent fashion, the EC50 value being 30 fold higher than that of isoproterenol. This effect on Isc was accompanied by the accumulation of intracellular cyclic AMP, and it was abolished by diphenylamine-2-carboxylate, bumetanide, and Cl-free medium, but not by amiloride. Pretreatment of cell with beta 1- and beta 2-adrenergic antagonists greatly reduced the Isc response to isoproterenol, whereas it had little effect on the BRL37344-induced response. In addition, the increase in Isc produced by BRL37344 was competitively antagonized by cyanopindolol, but pA2 was significantly different from the case of isoproterenol. These results suggest that beta 3-adrenergic receptors exist on airway epithelium, and may stimulate Cl secretion across the airway mucosa via accumulation of intracellular cyclic AMP.
First Department of Medicine, Tokyo Women's Medical College.
J
J
Tamaoki
M
M
Kondo
A
A
Chiyotani
F
F
Yamauchi
S
S
Takeuchi
K
K
Konno
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000502:physiology; D004983:Ethanolamines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; D002034:Bumetanide; C047975:cyanopindolol; C057368:BRL 37344; D010869:Pindolol; D000242:Cyclic AMP; D002118:Calcium