Differences in Ca2+ mobilization by muscarinic agonists in tracheal smooth muscle

M. H. Al-Hassani, J. G.N. Garcia, S. J. Gunst

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The muscarinic agonists acetylcholine (ACh) and McN-A-343 activate a homogeneous population of M3 receptors in canine tracheal smooth muscle. However, ACh is much more efficacious than McN-A-343 both at stimulating force development and active shortening and at antagonizing relaxation induced by isoproterenol. In other tissues, the same muscarinic receptor may be coupled to multiple subcellular pathways, but activate different pathways depending on the efficacy of the agonist. The present study investigated mechanisms of excitation-contraction coupling in canine tracheal smooth muscle by muscarinic agonists of different efficacy. ACh was more effective at stimulating inositol phosphate production and elicited a large initial transient increase in intracellular Ca2+ concentration ([Ca2+](i)), whereas McN-A-343 elicited only a slow gradual rise in [Ca2+](i). Extracellular Ca2+ influx through voltage-operated channels played a minor role in contractions induced by either agonist. Results suggest that contractions by ACh and McN-A-343 may be mediated by the same subcellular pathways; however, the greater potency of ACh at stimulating those pathways results in very different kinetics of Ca2+ activation.

Original languageEnglish (US)
Pages (from-to)L53-L59
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume264
Issue number1 8-1
StatePublished - Jan 1 1993
Externally publishedYes

Keywords

  • intracellular calcium
  • muscarinic receptor
  • receptor occupancy

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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