Details

Autor(en) / Beteiligte

• Quinn, Teresa
• Collins, Colm
• Baird, Alan W.

Titel

Mechanisms of neurokinin A‐ and substance P‐induced contractions in rat detrusor smooth muscle in vitro

Ist Teil von

• BJU international, 2004-09, Vol.94 (4), p.651-657

Ort / Verlag

Oxford, UK: Blackwell Science Ltd

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• 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% O2/5% CO2. 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 Ca2+‐free medium and significantly reduced by nifedipine (1 µmol/L). SKF‐96365 (60 µmol/L), an inhibitor of receptor‐mediated Ca2+ entry, abolished the nifedipine‐resistant response to substance P and carbachol, and significantly attenuated the response to neurokinin A. Depleting intracellular Ca2+ 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 Ca2+ influx largely through voltage‐operated and partly through receptor‐operated Ca2+ channels. Intracellular Ca2+ 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.