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

Chuen Mao Yang*, Sheng‐Ping ‐P Chou, Tsung‐Chang ‐C Sung

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

86 Scopus citations

Abstract

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. 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). 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‐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). 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. 1991 British Pharmacological Society

Original languageEnglish
Pages (from-to)613-618
Number of pages6
JournalBritish Journal of Pharmacology
Volume104
Issue number3
DOIs
StatePublished - 11 1991

Keywords

  • Smooth muscle
  • contraction
  • cyclic AMP
  • inositol phosphates
  • muscarinic receptor subtypes

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