Role of Rho-kinase in guinea-pig gallbladder smooth muscle contraction

Feb 28, 2006European journal of pharmacology

How Rho-kinase influences contraction of guinea pig gallbladder muscle

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Abstract

Y-27632 (10 µM) caused a significant decrease in basal resting tone and inhibited gallbladder contractions evoked by various stimuli.

Rho-kinase is involved in gallbladder smooth muscle contractions from both receptor-dependent and receptor-independent mechanisms.
Contractions induced by G-protein-coupled agonists carbachol and cholecystokinin were significantly inhibited by Y-27632.
Y-27632 also inhibited contractions resulting from thapsigargin and KCl additions.
The contractile response to calcium entry through store-operated channels and electrical field stimulation was significantly reduced by Y-27632.
Y-27632 did not significantly affect contractions triggered by the protein kinase C activator or the phosphatase inhibitor.

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Guinea-pig gallbladder smooth muscle contractions can be elicited pharmacologically by a range of mechanisms. The involvement of Rho-kinase in contractions mediated by receptor-dependent and receptor-independent mechanisms was investigated using the Rho-kinase inhibitor (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexane carboxamide (Y-27632). In a separate series of experiments, the role of Rho-kinase in the contractile response to Ca2+ entry through store-operated Ca2+ channels and to electrical field stimulation was also examined. Y-27632 (10 microM), which caused a significant decrease (P<0.0005) in basal resting tone, significantly inhibited gallbladder contractions evoked by cumulative additions of the G-protein-coupled agonists, carbachol (1 nM-100 microM; P<0.05) and cholecystokinin (10 nM-1 microM; P<0.005). Y-27632 also inhibited the contractions evoked by a single addition of the sarcoplasmic reticulum ATPase inhibitor, thapsigargin (1 microM; P<0.0005) and cumulative additions of KCl (10-85 mM; P<0.0005). The contractile response to Ca2+ entry through store-operated Ca2+ channels was significantly inhibited by Y-27632 (P<0.05) as were the contractile responses evoked by electrical field stimulation (2-25 Hz; P<0.0005). In contrast, Y-27632 had no significant effect on contractions evoked by phorbol 12,13-dibutyrate (0.1 nM-1 microM; a protein kinase C activator) or by the phosphatase inhibitor, cantharidin (100 microM). In conclusion, Rho-kinase contributes to the contractile response in guinea-pig gallbladder smooth muscle evoked by both G-protein-coupled and non-G-protein-coupled mechanisms in addition to contributing to the maintenance of basal tone. It also contributes to the contractile responses resulting from electrical field stimulation and store-operated Ca2+ channel entry.

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Role of Rho-kinase in guinea-pig gallbladder smooth muscle contraction

Abstract

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