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

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 (L_o) but not at 0.1L_o (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 1.0L_o 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.