Effects of cyclopiazonic acid on contractility and ecto-ATPase activity in guinea-pig urinary bladder and vas deferens.
1. 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, alpha,beta-methylene ATP (alpha,beta-MeATP), carbachol, noradrenaline (NA), histamine, and KCl; (2) to affect ecto-ATPase activity; (3) to modify the release of ATP evoked by EFS. 2. In the urinary bladder, CPA (10 microM) potentiated contractile responses to EFS, exogenous ATP (100 microM), alpha,beta-meATP (1 microM), carbachol (0.5 microM), histamine (30 microM) and KCl (30 mM). In the vas deferens, CPA (10 microM) potentiated responses to EFS, ATP, alpha,beta-meATP, NA (100 microM) and KCl. CPA at a concentration of 1 microM had no effect on ATP-induced relaxation of carbachol-precontracted guinea-pig taenia coli, and at a concentration of 10 microM it markedly increased spontaneous contractile activity of taenia. 3. Ecto-ATPase was estimated to have Vmax and Km values of 0.98 nmol Pi 30 min-1 mg-1 wet tissue and 881 microM ATP in the urinary bladder, and 0.75 nmol Pi 30 min-1 mg-1 wet tissue and 914 microM ATP in the vas deferens, respectively. CPA at a concentration of 10 microM significantly inhibited ecto-ATPase activity by 18% in the urinary bladder and by 24% in the vas deferens. 4. 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). 5. 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 Pu-purinoceptor-mediated responses since the contractile actions of all the agonists studied were potentiated to the same extent.
Department of Anatomy and Developmental Biology, University College London.
A U
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Ziganshin
C H
CH
Hoyle
L E
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Ziganshina
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G
Burnstock
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D014649:Vas Deferens / Q000187:drug effects / Q000201:enzymology / Q000502:physiology
D007211:Indoles; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C027201:ectoATPase; C000543:cyclopiazonic acid