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. 1995 Jan;114(1):127–137. doi: 10.1111/j.1476-5381.1995.tb14916.x

Effect of the Ca(2+)-ATPase inhibitor, cyclopiazonic acid, on electromechanical coupling in the guinea-pig ureter.

C A Maggi 1, S Giuliani 1, P Santicioli 1
PMCID: PMC1510167  PMID: 7536095

Abstract

1. We have investigated the effect of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase inhibitor, cyclopiazonic acid (CPA), on electromechanical coupling in the guinea-pig ureter. All experiments were performed in capsaicin-pretreated (10 microM for 15 min) ureters to prevent the release of sensory neuropeptides from afferent nerves. 2. In organ bath experiments, electrical field stimulation (EFS, 10 Hz for 1 s, 5 ms pulse width, 60 V) produced tetrodotoxin- (1 microM) resistant phasic contractions which were enhanced by Bay K 8644 (1 microM) and abolished by nifedipine (10-30 microM). 3. CPA (10 microM) enhanced the EFS-evoked contractions both in the absence and presence of Bay K 8644. The effect of CPA was concentration-dependent between 1 and 30 microM. The response to 10 microM CPA was biphasic: the maximal enhancement (58 +/- 3% increase) was observed within 10-20 min from CPA administration, followed by a decline to a new steady state (25 +/- 5% increase over baseline) at 50-60 min. The effect of CPA was reversed by washout. 4. Ryanodine (100 microM) produced a prompt enhancement of the EFS-evoked contractions of the guinea-pig ureter, which peaked at 42 +/- 3% increase over baseline; the co-administration of CPA (10 microM) and ryanodine (100 microM) produced a peak effect (60 +/- 8% enhancement) which was not different from that produced by CPA alone. With either ryanodine alone or ryanodine plus CPA, the enhancement of the EFS-induced contractions was biphasic, showing a time-course similar to that observed with CPA alone. Tetraethylammonium (10 mM) produced a significantly larger effect (93 +/- 13% increase over baseline) and its effect was sustained throughout the 60 min observation period. 5. In the presence of Bay K 8644, superfusion for 30 min with a low Na+ medium (60% of extracellular Na+ replaced by Li+ or choline) reduced the amplitude of EFS-evoked contractions by 20-35%. In both Li(+)- and choline-substituted media, spontaneous activity developed during superfusion with low Na+ Krebs solution which was suppressed by 10 microM nifedipine. CPA (10 microM) produced a marked enhancement of the EFS-evoked contractions in low-Na+ medium (both Li(+)- and choline-substituted) and this effect was sustained throughout the 60 min observation period.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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