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Mechanisms of neurokinin A‐ and substance P‐induced contractions in rat detrusor smooth muscle in vitro
Author(s) -
Quinn Teresa,
Collins Colm,
Baird Alan W.
Publication year - 2004
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.2004.05017.x
Subject(s) - carbachol , neurokinin a , substance p , endocrinology , chemistry , medicine , muscarinic agonist , muscarinic acetylcholine receptor , agonist , neurokinin b , nifedipine , neuropeptide , biology , receptor , calcium
OBJECTIVE To investigate the mechanisms of neurokinin A‐ and substance P‐induced contractions of rat urinary bladder smooth muscle, and to compare them with those of the muscarinic agonist carbachol. MATERIALS AND METHODS Rat urinary bladder strips were suspended under 1 g of tension in a physiological buffer at 37 °C, gassed with 95% O 2 /5% CO 2 . Mechanical activity was recorded isometrically during exposure to neurokinin A and substance P. RESULTS Both agents produced concentration‐dependent contractions of smooth muscle strips which were unaffected by tetrodotoxin (1 µmol/L), peptidase inhibitors (captopril, thiorphan and bestatin; 1 µmol/L each) or piroxicam (10 µmol/L). The rank order of potency of agonists was neurokinin A > substance P > carbachol. Contractile responses to neurokinin A and substance P, like the contractile responses to carbachol, were abolished in a nominally Ca 2+ ‐free medium and significantly reduced by nifedipine (1 µmol/L). SKF‐96365 (60 µmol/L), an inhibitor of receptor‐mediated Ca 2+ entry, abolished the nifedipine‐resistant response to substance P and carbachol, and significantly attenuated the response to neurokinin A. Depleting intracellular Ca 2+ stores with thapsigargin (1 µmol/L) significantly attenuated neurokinin A‐induced contractions but had no effect on substance P‐ or carbachol‐ induced contractions. The Rho‐kinase inhibitor, Y‐27632 (10 µmol/L), significantly reduced both phasic and tonic components of the contractile responses to neurokinin A, substance P and carbachol. CONCLUSION The contractile responses induced by tachykinins in rat urinary bladder smooth muscle strips involve a direct action on smooth muscle and are not modulated by peptidases or prostanoids. Neurokinin A and substance P, like carbachol‐induced contractions, depend on extracellular Ca 2+ influx largely through voltage‐operated and partly through receptor‐operated Ca 2+ channels. Intracellular Ca 2+ release contributes to the contractile response to neurokinin A but appears to have no involvement in substance P‐ and carbachol‐induced contractions. Rho‐kinase activation contributes to contractions induced by substance P, neurokinin A and carbachol.