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M 1 and M 3 muscarinic receptors in human pulmonary arteries
Author(s) -
Norel X.,
Walch L.,
Costantino M.,
Labat C.,
Gorenne I.,
Dulmet E.,
Rossi F.,
Brink C.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15688.x
Subject(s) - muscarinic acetylcholine receptor , cardiology , medicine , receptor
1 Acetylcholine (ACh) and the M 1 agonists (McN‐A‐343 or PD142505) relaxed human isolated pulmonary arteries which were pre‐contracted with noradrenaline (10 μ m ). In preparations where the endothelium had been removed ACh induced a contractile response whereas the M 1 agonists (McN‐A‐343 or PD142505) had no effect. 2 ACh‐ and McN‐A‐343‐induced relaxations were abolished after treatment of endothelium‐intact preparations with the drug combination N G ‐nitro‐L‐arginine (L‐NOARG: 0.1 mM) and indomethacin (1.7 μ m ). 3 The affinity (p K B value) for pirenzepine was higher in human pulmonary arteries when tissues were relaxed with McN‐A‐343 as compared with ACh (p K B values, 7.71 ± 0.30 ( n = 4) and 6.68 ± 0.15 ( n = 8), respectively). In addition, the affinity for pFHHSiD 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 methoctramine in human isolated pulmonary arteries with the endothelium either intact or removed, suggested the lack of involvement of M 2 and M 4 receptors in the ACh responses. 5 Phenoxybenzamine (3 μ m : 30 min) abolished both ACh contraction and relaxation in human pulmonary artery. The ACh contraction was present when the phenoxybenzamine treatment was preceded by incubation with pFHHSiD (2 μ m ) but not with pirenzepine (1 μ m ). In addition, the ACh relaxation was present when preparations were treated with either pFHHSiD (2 μ m ) or pirenzepine (1 μ m ), before exposure to phenoxybenzamine. 6 These results in human isolated pulmonary arteries support the notion that only M 3 receptors, on smooth muscle, mediate the ACh‐induced contraction whereas M 3 and M 1 receptors are involved in the endothelium‐dependent ACh‐induced relaxation.