Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The aim of this study was to assess the role of sarcoplasmic reticulum (SR) calcium (Ca2+) in the smooth muscle relaxant and hyperpolarizing actions of calcitonin gene-related peptide (CGRP) in the guinea-pig ureter. 2. CGRP (0.1 microM) rapidly and transiently reduced myogenic phasic contractions (twitches) produced by electrical field stimulation (EFS). Approximately 70% of the response to CGRP was antagonized by glibenclamide (1 microM). 3. Cyclopiazonic acid (CPA, 10 microM), ryanodine (100 microM) and thapsigargin (1 microM) reduced only the glibenclamide-sensitive component of the response to CGRP (0.1 microM) but did not modify the mechano-inhibitory effect of cromakalim (3 microM). A low concentration of CPA (1 microM), assumed to produce a limited impairment of Ca2+ uptake from the stores, prolonged the duration of the inhibitory response to CGRP. Pre-exposure to caffeine (5 mM) inhibited the suppression of twitches by CGRP or cromakalim. 4. When the frequency of EFS was increased, the suppression of twitches by CGRP was reduced. Under these conditions, CPA (1 microM) again prolonged the duration of the inhibitory response to CGRP. 5. CGRP (0.1 microM) and cromakalim (3 microM) markedly depressed the phasic component of contractions to 80 mM KCl. CPA (10 microM) antagonized the inhibitory effect of CGRP but not that of cromakalim. Inhibition of the tonic contraction to 80 mM KCl by CGRP was insensitive to CPA. 6. In sucrose gap experiments, a 5 min exposure to CGRP (0.1 microM) or cromakalim (3 microM) produced a sustained membrane hyperpolarization. Caffeine (5 mM) produced a glibenclamide-sensitive transient hyperpolarization followed by a sustained depolarization. When tested in a Ca(2+)-free medium the hyperpolarization produced by CGRP, cromakalim or caffeine was reduced. In normal Krebs, pre-exposure to CPA (10 microM, 60 min) only abolished the hyperpolarization induced by CGRP. In contrast, 5 min after a caffeine challenge (5 mM) the hyperpolarizations induced by CGRP or cromakalim were reduced. The CGRP-induced hyperpolarization was insensitive to apamin (0.1 microM) or charybdotoxin (0.1 microM). 7. We conclude that the K channel-opening action of CGRP in the guinea-pig ureter requires the mobilization of intracellular Ca2+ from a caffeine- and CPA-sensitive store, leading to transient activation of glibenclamide-sensitive K channels. The K channel-opening action of caffeine appears to involve Ca2+ mobilization from a store which is insensitive to depletion by CPA.
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PMID:Role of intracellular Ca2+ in the K channel opener action of CGRP in the guinea-pig ureter. 883 77

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