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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the effect of the dihydropyridine calcium channel agonist, Bay K 8644, and of the plant alkaloid blocker of calcium-induced calcium release (CICR) from the sarcoplasmic reticulum, ryanodine, on the refractory period, action potential and mechanical response of the guinea-pig isolated ureter to electrical stimulation. All experiments were performed in ureters pre-exposed to 10 microM capsaicin to eliminate the inhibitory influence exerted by local release of sensory neuropeptides on ureteral excitability and contraction. In organ bath experiments, electrical field stimulation with parameters which produce direct excitation of ureteral smooth muscle (train of pulses at 10 Hz, 5 ms pulse width, 60 V for 1 s) produced tetrodotoxin- (1 microM) resistant phasic contractions. The response to EFS was abolished by nifedipine (1 nM-3 microM) and was enhanced by Bay K 8644 (1 nM-3 microM). In the presence of Bay K 8644 (1 microM), nifedipine (30 microM) abolished the evoked contractions. Ryanodine (10-100 microM) had no significant effect on the amplitude of evoked contraction. The response of the guinea-pig ureter to direct electrical stimulation of smooth muscle is characterized by a refractory period: at least 40 s interstimulus interval was required to produce a second response in all preparations tested. Bay K 8644 (1 microM) markedly reduced the refractory period of the ureter and a similar effect was observed with ryanodine (100 microM). To further analyze the effect of Bay K 8644 and ryanodine on the refractory period, the response of the ureter was investigated over a 10 s period of stimulation (other parameters as above). In control ureters, continuous stimulation for 10 s produced only one phasic contraction just after the beginning of the train of stimuli. In the presence of Bay K 8644 or ryanodine, more than one phasic contraction developed during a 10 s stimulation, i.e. the refractory period became shorter than the train duration. When both Bay K 8644 and ryanodine were tested on the same preparations, an additive excitatory effect was observed on the mechanical response to electrical stimulation. A slight elevation of KCl concentration (5-10 mM) reduced the refractory period of the ureter as observed with ryanodine or Bay K 8644. Application of KCl (80 mM) produced a biphasic contractile response of the ureter: a series of phasic contractions occurred first, which were then replaced by a slowly developing tonic response. Bay K 8644 (1 microM) enhanced both components of the response to KCl. Ryanodine (10 and 100 microM) markedly prolonged the duration of phasic contractions evoked by KCl and, at 100 microM, slightly (about 25%) reduced the amplitude of tonic contraction.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of Bay K 8644 and ryanodine on the refractory period, action potential and mechanical response of the guinea-pig ureter to electrical stimulation. 752 May 36

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. 6. In the absence of Bay K 8644, the response of the ureter smooth muscle to EFS is characterized by a refractory period: an interval of about 30 s was required between two applied stimuli to produce a second response comparable in size to that elicited by the first stimulus. CPA (10 micro M, 10-20 min before)markedly reduced the refractory period of the guinea-pig ureter to EFS.7. CPA (10 micro M, 30-60 min before) increased the phasic component of contraction produced by 80 m MKCl. The tonic component of the response to KCl was slightly but not significantly reduced by CPA,and a 'hump' in the tonic contraction was observed at 1-2 min from addition of KCl.8. In sucrose gap experiments, 10 micro M CPA produced a sustained depolarization of the membrane and reduced the latency between application of electrical stimuli and onset of the action potential; these effects were maintained throughout the 60 min superfusion with CPA. CPA also transiently prolonged the plateau phase of the action potential and increased the peak amplitude of contraction: these effects peaked at about 10-20 min from start of superfusion with CPA and then declined. At the peak of its enhancing effect on contraction amplitude, CPA prolonged the contractile phase of the contraction relaxation cycle.9.Superfusion with a low-Na, choline-substituted Krebs solution produced a reversible membrane depolarization. In the presence of Bay K 8644 (1 micro M), action potentials and phasic contractions were superimposed on this depolarization which were abolished by nifedipine (1O micro M).10. These findings indicate that CPA augments the excitability and affects the contraction-relaxation cycle of the smooth muscle of the guinea-pig ureter, implying a role for sarcoplasmic reticulum Ca2+-ATPase in the regulation of electromechanical coupling. The effects of CPA resemble those produced by ryanodine and the effect of the two agents on the amplitude of contractions is non-additive.It appears that following blockade of the CPA-sensitive SR Ca2+ pump, other mechanism(s) may come into action to reduce intracellular Ca2+. The Na+/Ca2+ exchanger could be involved in the compensatory changes responsible for the fading of the response to CPA.
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PMID:Effect of the Ca(2+)-ATPase inhibitor, cyclopiazonic acid, on electromechanical coupling in the guinea-pig ureter. 753 95

1. We have investigated the internal Ca2+ store and its ability to affect contraction by simultaneously measuring force and Ca2+ in the ureter from guinea-pig and rat. Both species responded in a similar manner to electrical stimulation and depolarization with high-K+, generating plateau-type action potentials and increasing intracellular calcium ([Ca2+]i) and force. 2. In the guinea-pig, carbachol had no effect on [Ca2+]i and force in the resting ureter. In contrast, resting rat ureter always responded with a large [Ca2+]i rise and maintained force to carbachol in Ca(2+)-containing solution, and in Ca(2+)-free solution it showed a transient increase in [Ca2+]i and force. This Ca2+ release and force development was also present in both polarized and high-K(+)-depolarized preparations and was insensitive to nifedipine, suggesting the presence of a receptor-coupled pathway of Ca2+ release in rat ureter. 3. Caffeine was able to produce a release of Ca2+ from the internal store of guinea-pig ureter and elicit contraction. However, rat ureter failed to respond to caffeine. In the presence of La3+, the caffeine response in the guinea-pig ureter and carbachol response in the rat ureter, elicited in Ca(2+)-free solutions, were always increased and prolonged and could be repeatedly evoked, suggesting similarity in Ca2+ uptake behaviour of the store in both species. 4. Ryanodine blocked the caffeine responses of the guinea-pig ureter elicited both in Ca(2+)-containing and Ca(2+)-free solutions, both in the absence and presence of La3+. However, ryanodine failed to prevent the rat ureter responding to carbachol, suggesting that carbachol was releasing Ca2+ from a ryanodine-insensitive channel in the sarcoplasmic reticulum (SR). 5. Cyclopiazonic acid, which inhibits the SR Ca(2+)-ATPase, abolished the effects of both caffeine and carbachol in Ca(2+)-free solutions in guinea-pig and rat, respectively. 6. We conclude that there is a major difference in the mechanisms of Ca2+ release in the internal Ca2+ store of smooth muscle from guinea-pig and rat ureter. The data suggest that the guinea-pig store is purely a calcium-induced calcium release (CICR)-type store and that the rat store is a pure receptor-operated Ca2+ store.
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PMID:Major difference between rat and guinea-pig ureter in the ability of agonists and caffeine to release Ca2+ and influence force. 884 29