EVIDENCE FOR AN ATYPICAL, OR BETA-3-ADRENOCEPTOR IN FERRET TRACHEAL EPITHELIUM

Citation
Se. Webber et Mj. Stock, EVIDENCE FOR AN ATYPICAL, OR BETA-3-ADRENOCEPTOR IN FERRET TRACHEAL EPITHELIUM, British Journal of Pharmacology, 105(4), 1992, pp. 857-862
Citations number
19
Language
INGLESE
art.tipo
Article
ISSN journal
0007-1188
Volume
105
Issue
4
Year of publication
1992
Pages
857 - 862
Database
ISI
SICI code
0007-1188(1992)105:4<857:EFAAOB>2.0.ZU;2-9
Abstract
1 A preparation of the ferret trachea in vitro was used to examine the effects of three selective beta-adrenoceptor agonists on lysozyme sec retion from submucosal gland serous cells and epithelial albumin trans port into tracheal mucus following sustained, submaximal stimulation o f mucus production with methacholine (20-mu-M) 2 Prenalterol, salbutam ol and BRL 37344 all enhanced methacholine-induced albumin output. BRL 37344 was 10,000 times more potent than salbutamol, and salbutamol wa s slightly more potent than prenalterol. The concentrations required t o increase albumin output by 100% (EC100%) were 1.4 nM, 0.7 mM and app roximately 1.0 mM for BRL 37344, salbutamol and prenalterol, respectiv ely. All three agonists inhibited methacholine-induced lysozyme output , with salbutamol being 60 times more potent than BRL 37344, and BRL 3 7344 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 was much more po tent at inhibiting the response to salbutamol; the pA2 for ICI 118551 was 5.55 and 7.18 (P < 0.001) when the agonist was BRL 37344 and salbu tamol, respectively. ICI 118551 also attentuated the inhibition of lys ozyme output produced by the two agonists, but was 10-30 times more po tent at inhibiting this response than the albumin response to BRL 3734 4 and salbutamol. 4 The greater potency (4-5 orders of magnitude) of B RL 37344, compared to the beta(1)-(prenalterol) and beta(2) - (salbuta mol) adrenoceptor selective agonists, in stimulating methacholine-indu ced albumin transport suggests that tracheal epithelium possess an aty pical, 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. In hibition of methacholine-induced serous cell lysozyme output would app ear to be mediated predominantly by beta(2)-adrenoceptors. 5 In view o f the possible beneficial protective effects of albumin in airway surf ace liquid, selective beta(3)-agonists like BRL 37344 might have poten tial value in the prevention and/or treatment of inflammatory airway d isease.