Linear dependence of muscarinic receptor-mediated phosphatidylinositol turnover on muscle length and its pharmacodynamics in airway smooth muscle

Steven An, C. M. Hai

Research output: Contribution to journalArticle

Abstract

Phosphatidylinositol (PI) turnover is an important signal transduction mechanism coupled to muscarinic receptor in airway smooth muscle. Previously, we have shown a significant increase in PI turnover in bovine tracheal smooth muscle activated by 1 uM carbachol (a muscarinic agonist) at optimal length (Lo) but not at 0.1Lo (AJP 267: C1657, 1994). In current study, we tested the hypothesis that carbachol-activated PI turnover is a continuous function of muscle length. We labelled bovine tracheal smooth muscle strips with 3H-inositol (I) and measured the 30-min accumulation of 3H-IP1, 3H-IP2, and 3H-IP3 in carbachol-activated and control tissues at 0.2, 0.6, and 1.0Lo using anion-exchange chromatography. We found that suprabasal product ions of H-IP1 and 3H-IP2 induced by 1 uM carbachol were both linearly dependent on muscle length. As expected, 3H-IP3 production was not significant at 30 min after activation by carbachol. Since the same [carbachol] was used at all lengths, these results suggest that PI turnover is not only dependent on agonist concentration, but also modulated by muscle length. Additional experiments will be performed to determine whether muscle length modulates total number or binding affinity of the muscarinic receptors in airway smooth muscle.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - 1997
Externally publishedYes

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Pharmacodynamics
carbachol
phosphatidylinositols
Carbachol
Muscarinic Receptors
pharmacology
Phosphatidylinositols
smooth muscle
Smooth Muscle
Muscle
Muscles
muscles
receptors
agonists
Muscarinic Agonists
cattle
Inositol
Signal transduction
Anions
signal transduction

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

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abstract = "Phosphatidylinositol (PI) turnover is an important signal transduction mechanism coupled to muscarinic receptor in airway smooth muscle. Previously, we have shown a significant increase in PI turnover in bovine tracheal smooth muscle activated by 1 uM carbachol (a muscarinic agonist) at optimal length (Lo) but not at 0.1Lo (AJP 267: C1657, 1994). In current study, we tested the hypothesis that carbachol-activated PI turnover is a continuous function of muscle length. We labelled bovine tracheal smooth muscle strips with 3H-inositol (I) and measured the 30-min accumulation of 3H-IP1, 3H-IP2, and 3H-IP3 in carbachol-activated and control tissues at 0.2, 0.6, and 1.0Lo using anion-exchange chromatography. We found that suprabasal product ions of H-IP1 and 3H-IP2 induced by 1 uM carbachol were both linearly dependent on muscle length. As expected, 3H-IP3 production was not significant at 30 min after activation by carbachol. Since the same [carbachol] was used at all lengths, these results suggest that PI turnover is not only dependent on agonist concentration, but also modulated by muscle length. Additional experiments will be performed to determine whether muscle length modulates total number or binding affinity of the muscarinic receptors in airway smooth muscle.",
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