Effects of cyclopiazonic acid on contractility and ecto‐ATPase activity in guinea‐pig urinary bladder and vas deferens

Abstract

Cyclopiazonic acid (CPA), an inhibitor of sarcoplasmic ATPase, was tested on guinea‐pig urinary bladder and vas deferens for its ability: (1) to modify contractile responses to electrical field stimulation (EFS), exogenous ATP, α,β‐methylene ATP (α,β‐meATP), carbachol, noradrenaline (NA), histamine, and KCl; (2) to affect ecto‐ATPase activity; (3) to modify the release of ATP evoked by EFS. In the urinary bladder, CPA (10 μm) potentiated contractile responses to EFS, exogenous ATP (100 μm), α,β‐meATP (1 μm), carbachol (0.5 μm), histamine (30 μm) and KCl (30 μm). In the vas deferens, CPA (10 μm) potentiated responses to EFS, ATP, α,β‐meATP, NA (100 μm) and KCl. CPA at a concentration of 1 μm had no effect on ATP‐induced relaxation of carbachol‐precontracted guinea‐pig taenia coli, and at a concentration of 10 μm it markedly increased spontaneous contractile activity of taenia. Ecto‐ATPase was estimated to have Vmax and Km values of 0.98 nmol Pi 30 min−1 mg−1 wet tissue and 881 μm ATP in the urinary bladder, and 0.75 nmol Pi 30 min−1 mg−1 wet tissue and 914 μm ATP in the vas deferens, respectively. CPA at a concentration of 10 μm significantly inhibited ecto‐ATPase activity by 18% in the urinary bladder and by 24% in the vas deferens. In the guinea‐pig vas deferens, CPA significantly potentiated ATP release evoked by EFS from 2.2 ± 0.8 (6) pmol ATP min−1 g−1 wet tissue to 35.2 ± 4.8 (6) pmol ATP min−1 g−1 wet tissue (P < 0.01). In conclusion, the potentiation of contractile responses of the guinea‐pig urinary bladder and vas deferens by CPA has a non‐specific character. CPA inhibited ecto‐ATPase activity and increased ATP release, but these effects do not appear to contribute to the potentiation of P2x‐purinoceptor‐mediated responses since the contractile actions of all the agonists studied were potentiated to the same extent. 1994 British Pharmacological Society