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Y‐27632 relaxation of carbachol‐induced smooth muscle contraction in guinea pig trachea
Author(s) -
Hare Brendan,
Kojtari Sheri,
Herrera Gerald M.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.781.2
Subject(s) - carbachol , contractility , muscarinic agonist , contraction (grammar) , muscarinic acetylcholine receptor , agonist , medicine , endocrinology , rho associated protein kinase , muscle contraction , chemistry , guinea pig , acetylcholine , stimulation , biology , kinase , receptor , biochemistry
Smooth muscle (SM) contractions are caused by increases in cytoplasmic Ca 2+ ([Ca 2+ ] i ). SM contractility may also depend on factors that regulate the sensitivity of intracellular processes to [Ca 2+ ] i . Increasing evidence supports a role for Rho Kinase pathway in regulating smooth muscle contractility, and modulation of Rho Kinase activity may have therapeutic use for diseases such as asthma. Pharmacological inhibition of Rho Kinase using Y‐27632 causes relaxation of airway smooth muscle preparations. However, little is known about how Rho Kinase inhibition affects the sensitivity of airway smooth muscle to a contractile agonist. In this study, the muscarinic agonist carbachol (CCh) was applied to guinea pig trachea rings in a cumulative fashion. Following an initial CCh dose‐response curve, a second CCh dose‐response curve was constructed in the presence of varying concentrations of Y‐27632 (0.01 to 100 µM). EC 50 values for CCh‐induced contractions in the presence of Y‐27632 were (in µM) 0.52, 0.4, 0.15, 0.2, 0.24, 0.29, 2, 0.51, 2.2, 0.46 in presence of 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 Y‐27632, respectively. The maximum contractile response to CCh was decreased by 20‐25% in the presence of Y‐27632. Inhibition of Rho Kinase using Y‐27632 appears to decrease the maximum contractility in response to muscarinic stimulation without affecting the sensitivity of the airway SM to the muscarinic agonist.