Muscarinic receptor subtypes coupled to generation of different second messengers in isolated tracheal smooth muscle cells

• Published in: British journal of pharmacology Vol. 104; no. 3; pp. 613 - 618
• Main Authors: Yang, Chuen Mao, Chou, Sheng‐Ping, Sung, Tsung‐Chang
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.1991; Nature Publishing
• Subjects: Adenylyl Cyclase Inhibitors; Air breathing; Animals; Binding, Competitive - drug effects; Biological and medical sciences; Carbachol - pharmacology; contraction; cyclic AMP; Cyclic AMP - biosynthesis; Dogs; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; inositol phosphates; muscarinic receptor subtypes; Muscle, Smooth - cytology; Muscle, Smooth - drug effects; Parasympatholytics - pharmacology; Phosphatidylinositols - pharmacology; Receptors, Muscarinic - drug effects; Respiratory system: anatomy, metabolism, gas exchange, ventilatory mechanics, respiratory hemodynamics; Second Messenger Systems - drug effects; Signal Transduction - drug effects; Smooth muscle; Trachea - cytology; Trachea - drug effects; Vertebrates: respiratory system; Fissipedia; Carnivora; Cyclic AMP; Smooth muscle; Inositol phosphate; Respiratory system; Muscle contraction; In vitro; Vertebrata; Mammalia; Animal; Second messenger; Muscarinic receptor; Dog; Trachea
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1991.tb12478.x

1 Activation of muscarinic receptor subtypes leads to contraction, an increase in the accumulation of inositol phosphates (IPs) and a decrease in adenosine 3′: 5′‐cyclic monophosphate (cyclic AMP) synthesis in tracheal smooth muscle. The concentrations of carbachol that produced a half‐maximal effect (EC50) in inhibition of cyclic AMP generation, stimulation of IPs formation and contraction were 15 nm, 2.0 μm and 0.17 μm, respectively. 2 Pirenzepine, a selective M1 antagonist, displayed a low affinity for antagonizing cyclic AMP inhibition, IPs formation and contraction induced by carbachol (pKB = 6.8, 7.0, and 7.1, respectively). 3 Methoctramine, a cardioselective M2 antagonist, blocked cyclic AMP inhibition with a high affinity (pKB = 7.5), while it antagonized IPs formation and contraction with a low affinity (pKB = 6.2 and 6.1, respectively). 4 4‐Diphenylacetoxy‐n‐methylpiperidine (4‐DAMP), a selective smooth muscle M3 antagonist, possessed a high affinity in blocking IPs formation (pKB = 8.8) and contraction (pKB = 9.2) as well as a low affinity for antagonism of cyclic AMP inhibition (pKB = 8.1). 5 In conclusion, we have demonstrated that M2 and M3 receptor subtypes are coupled to different effector systems in tracheal smooth muscle. An M1 receptor subtype is not involved in the generation of the second messengers examined. Inhibition of cyclic AMP formation may be coupled to the M2 receptor subtype. The accumulation of IPs and presumably IP‐induced Ca2+ release may function as the transducing mechanism for cholinergic contraction of tracheal smooth muscle through the activation of M3 receptors.