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Involvement of Rho kinase and protein kinase C in carbachol‐induced calcium sensitization in β ‐escin skinned rat and guinea‐pig bladders
Author(s) -
DurluKandilci N Tugba,
Brading Alison F
Publication year - 2006
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706723
Subject(s) - carbachol , guinea pig , calcium , sensitization , contraction (grammar) , calmodulin , endocrinology , medicine , chemistry , biology , stimulation , immunology
1 The signal transduction pathways involved in carbachol (CCh)‐induced calcium sensitization in β ‐escin permeabilized rat and guinea‐pig bladder smooth muscles were investigated and the results were compared with guinea‐pig taenia caecum. 2 Calcium contractions elicited cumulatively ( p Ca 7.5–5) in the presence of calmodulin were significantly increased in all three tissues when CCh (50 μ M ) was added to the medium. 3 Under constant [Ca 2+ ] i conditions ( p Ca 6), calmodulin (1 μ M ) and then GTP (100 μ M ) initiated significant contractions. CCh (50 μ M ) added to the bath caused a further contraction in all three tissues – calcium sensitization. This sensitization was significantly inhibited by atropine (50 μ M ). 4 The incubation of the tissues with the IP 3 ‐receptor blocker 2‐APB (30 μ M ) reduced the subsequent development of calcium sensitization by CCh in rat bladder but did not affect it in guinea‐pig bladder and taenia ceacum. 5 The Rho kinase (ROK) inhibitor Y‐27632 (5 μ M ) added in the presence of CCh reversed the calcium sensitization in rat bladder, whereas a transient contraction followed by a relaxation to a level not significantly different from the CCh contraction was seen in both guinea‐pig bladder and taenia caecum. Y‐27632 (1 μ M ) continuously present significantly inhibited the CCh‐induced Ca 2+ sensitization in rat bladder but not in guinea‐pig bladder or taenia caecum. 6 In the presence of cyclopiazonic acid (CPA) (1 μ M ) and calmodulin (1 μ M ), Y‐27632 (5 μ M ) did not change the calcium response curve (3 × 10 −7 –10 −5 M ) in rat bladder but increased the contractile responses significantly in both guinea‐pig bladder and taenia caecum. 7 The protein kinase C (PKC) inhibitor GF 109203X (5 μ M ) added in the presence of CCh inhibited the calcium sensitization induced by this muscarinic agonist in all three tissues in different ratios. 8 In conclusion, muscarinic receptor activation induces calcium sensitization in rat and guinea‐pig detrusor smooth muscles but there are differences in their pathways.British Journal of Pharmacology (2006) 148 , 376–384. doi: 10.1038/sj.bjp.0706723