Evidence for an atypical, or beta 3-adrenoceptor in ferret tracheal epithelium.
1. A preparation of the ferret trachea in vitro was used to examine the effects of three selective beta-adrenoceptor agonists on lysozyme secretion from submucosal gland serous cells and epithelial albumin transport into tracheal mucus following sustained, submaximal stimulation of mucus production with methacholine (20 microM). 2. Prenalterol, salbutamol and BRL 37344 all enhanced methacholine-induced albumin output. BRL 37344 was 10,000 times more potent than salbutamol, and salbutamol was slightly more potent than prenalterol. The concentrations required to increase albumin output by 100% (EC100%) were 1.4 nM, 0.7 mM and approximately 1.0 mM for BRL 37344, salbutamol and prenalterol, respectively. All three agonists inhibited methacholine-induced lysozyme output, with salbutamol being 60 times more potent than BRL 37344, and BRL 37344 being approximately 100 times more potent than prenalterol. 3. The selective beta 2-adrenoceptor antagonist, ICI 118551, inhibited the increase in albumin output produced by BRL 37344, but much more potent at inhibiting the response to salbutamol; the pA2 for ICI 118551 was 5.55 and 7.18 (P less than 0.001) when the agonist was BRL 37344 and salbutamol, respectively. ICI 118551 also attenuated the inhibition of lysozyme output produced by the two agonists, but was 10-30 times more potent at inhibiting this response than the albumin response to BRL 37344 and salbutamol. 4. The greater potency (4-5 orders of magnitude) of BRL 37344, compared to the beta 1- (prenalterol) and beta 2- (salbutamol) adrenoceptor selective agonists, in stimulating methacholine-induced albumin transport suggests that tracheal epithelium possess an atypical, or beta 3-adrenoceptor similar to that previously reported for adipocytes and gastrointestinal smooth muscle. The weak antagonism of the response to BRL 37344 by ICI 118551 would also be consistent with an atypical adrenoceptor mediating the albumin transport response. Inhibition of methacholine-induced serous cell lysozyme output would appear to be mediated predominantly by beta2-adrenoceptors.5. In view of the possible beneficial protective effects of albumin in airway surface liquid, selective beta3-agonists like BRL 37344 might have potential value in the prevention and/or treatment of inflammatory airway disease.
Webber
S E
SE
Department of Physiology, St. George's Hospital Medical School, Tooting, London.
Stock
M J
MJ
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000418:Albumins / Q000378:metabolism; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004848:Epithelium / Q000378:metabolism; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D005289:Ferrets; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009113:Muramidase / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D014132:Trachea / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000418:Albumins; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D016210:Methacholine Chloride; C026777:ICI 118551; C057368:BRL 37344; D009113:Muramidase; D000420:Albuterol