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
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.