Af. Roffel et al., CHOLINERGIC CONTRACTION OF THE GUINEA-PIG LUNG STRIP IS MEDIATED BY 9USCARINIC M(2)-LIKE RECEPTORS, European journal of pharmacology, 250(2), 1993, pp. 267-279
The muscarinic receptor subtype mediating contraction of the guinea pi
g lung strip preparation was investigated and compared with that in gu
inea pig tracheal and human peripheral airway (small bronchi) smooth m
uscle preparations, using a number of subtype selective muscarinic rec
eptor antagonists. It was found that guinea pig lung strip contraction
was not mediated by a homogenous class of muscarinic M3 receptors, in
contrast to guinea pig tracheal and human peripheral airway smooth mu
scle. The affinities of the M1- and M3/M2-selective muscarinic recepto
r antagonists on the guinea pig lung strip were between 0.35 and 1.94
log units lower than in the M3 receptor tissues (respective pA2 values
on guinea pig lung strip and trachea: pirenzepine 6.36/6.71, AF-DX 47
4 6.39/7.11, AQ-RA 721 6.93/7.96, DAU 5884 6.78/8.72, UH-AH 371 7.04/8
.20), whereas the affinities of the M2/M3-selective antagonists were b
etween 0.63 and 1.97 log units higher (AF-DX 116 6.63/6.00, AQ-RA 741
7.48/6.63, gallamine 5.44/3.47, methoctramine 7.30/5.38). As a result,
a good correlation was obtained when pA2 values from guinea pig lung
strip were compared to pK(i) values towards bovine cardiac muscarinic
M2 receptors, though it was noticed that pirenzepine and the M3/M2-sel
ective antagonists showed a closer relationship than the M2-selective
compounds. These results suggest that cholinergic contraction of the g
uinea pig lung strip is mediated by muscarinic M2-like receptors, poss
ibly representing a novel subtype or a mixture of M2 (cardiac) and M3
(or M4) subtypes. It remains to be established, however, on what struc
ture in the lung these contractile M2-like receptors are located and a
lso by which transduction mechanism they produce contraction.