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Synergistic effects in neuromuscular activation and calcium‐sensitization in the bladder trigone
Author(s) -
Roosen Alexander,
Wu Changhao,
Sui GuiPing,
Fry Christopher H.
Publication year - 2008
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2007.07351.x
Subject(s) - carbachol , purinergic receptor , muscarinic acetylcholine receptor , phenylephrine , endocrinology , chemistry , medicine , trigone of urinary bladder , stimulation , protein kinase c , receptor , urinary bladder , kinase , biochemistry , blood pressure
OBJECTIVE To elucidate possible synergistic effects between adrenergic, muscarinic, and purinergic neuromuscular activation in the bladder trigone, and to examine the relevance of the Rho‐kinase (ROCK)/protein kinase C (PKC) pathway as a possible underlying mechanism. MATERIALS AND METHODS Muscle strips were dissected from the superficial trigone of male guinea‐pigs. Contractions were elicited by electrical‐field stimulation (EFS: 0.1 ms pulses, 1–64 Hz for 3 s) or exposure to exogenous agonists. RESULTS There was evidence for functional adrenergic, purinergic, and muscarinic neurotransmission. Selective inhibition of individual components suggested synergistic interactions. The mean ( sd ) EFS contractions were enhanced by carbachol (0.3 µ m ) and phenylephrine (10 µ m ) to 2.4 (0.4) and 6.4 (1.5)‐fold of control (32 Hz), respectively. Phenylephrine (10 µ m ) also augmented contractions induced by carbachol (1 µ m ) to 3.9 (1.2)‐fold of control, α,β‐methylene ATP (1 µ m ) to 4.3 (0.4) and 20 m m superfusate K + to 5.0 (2.0). The PKC inhibitors GF 109203X (5 µ m ) and H‐7 (100 µ m ), as well as the ROCK inhibitor Y‐27632 (5 µ m ) reduced the phenylephrine contracture to 37.3 (7.4), 38.5 (11.2) and 54.9 (7.8)% of control, respectively. With the exception of H‐7 they had no significant effect on the carbachol response. CONCLUSION This study shows a synergistic effect between adrenergic, muscarinic, and purinergic receptor activation on the muscle of the superficial trigone. The study suggests that Ca 2+ ‐sensitization of contractile proteins plays a key role in this synergism, particularly for adrenergic activation.