1 Acetylcholine (ACh) and the M(1) agonists (McN-A-343 or PD142505) re
laxed human isolated pulmonary arteries which were pre-contracted with
noradrenaline (10 mu M). In preparations where the endothelium had be
en removed ACh induced a contractile response whereas the M(1) agonist
s (McN-A-343 or PD142505) had no effect. 2 ACh- and McN-A-343-induced
relaxations were abolished after treatment of endothelium-intact prepa
rations with the drug combination N-G-nitro-L-arginine (L-NOARG: 0.1 m
M) and indomethacin (1.7 mu M). 3 The affinity (pK(B) value) for piren
zepine was higher in human pulmonary arteries when tissues were relaxe
d with McN-A-343 as compared with ACh (pK(B) values, 7.71+/-0.30 (n=4)
and 6.68+/-0.15 (n=8), respectively). In addition, the affinity for p
FHHSiD against McN-A-343- and ACh-induced relaxations was 6.86+/-0.13
(n=3) and 7.35+/-0.11 (n=9), respectively. 4 The low affinities for me
thoctramine in human isolated pulmonary arteries with the endothelium
either intact or removed, suggested the lack of involvement of M(2) an
d M(4) receptors in the ACh responses. 5 Phenoxybenzamine (3 mu M: 30
min) abolished both ACh contraction and relaxation in human pulmonary
artery. The ACh contraction was present when the phenoxybenzamine trea
tment was preceded by incubation with pFHHSiD (2 mu M) but not with pi
renzepine (1 mu M). In addition, the ACh relaxation was present when p
reparations were treated with either pFHHSiD (2 mu M) or pirenzepine (
1 mu M), before exposure to phenoxybenzamine. 6 These results in human
isolated pulmonary arteries support the notion that only M(3) recepto
rs, on smooth muscle, mediate the ACh-induced contraction whereas M(3)
and M(1) receptors are involved in the endothelium-dependent ACh-indu
ced relaxation.