| Effects of midazolam on intracellular Ca2+ and tension in airway smooth muscles. | |
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MedLine Citation:
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PMID: 7486152 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: It has been demonstrated that a group of minor tranquilizers, benzodiazepines, are able to relax airway smooth muscles. To determine the underlying mechanisms of this phenomenon, the effects of midazolam on the intracellular Ca2+ concentration ([Ca2+]i) and tension in airway smooth muscles were investigated. METHODS: Using front-surface fluorometry and fura-2-loaded porcine tracheal smooth muscle strips, both [Ca2+]i and isometric tension developments were simultaneously recorded. RESULTS: When the tracheal strips were exposed to a high external K(+)-solution (40 mM) or 10(-7) M carbachol containing 1.25 mM Ca2+, both [Ca2+]i and tension increased rapidly until they reached a plateau (the steady state). During steady-state contraction induced by K(+)-depolarization or carbachol, the cumulative application of midazolam (10(-7) approximately 10(-4) M) caused decreases in both [Ca2+]i and tension, in a concentration-dependent manner. During 40 mM K(+)-induced depolarization, the stepwise increases in the extracellular Ca2+ concentration induced the stepwise increases in [Ca2+]i and tension. Midazolam (3 x 10(-5) M) inhibited these increases in [Ca2+]i and tension, but had no effect on the [Ca2+]i-tension relationship. In the presence of 3 x 10(-3) M NiCl2 (a nonselective cation channel blocker), midazolam (3 x 10(-5) M) did not cause any additional reduction of [Ca2+]i or tension during the contraction induced by carbachol (10(-7) M). In the absence of extracellular Ca2+, midazolam (3 x 10(-5) M) had no effect on the transient increases in either [Ca2+]i or the tension induced by carbachol (10(-7) M) or caffeine (20 mM). Pretreatment with both 10(-5) M flumazenil (a specific central antagonist of benzodiazepines) and 10(-5) M PK11195 (a specific peripheral antagonist of benzodiazepines) did not influence the effect of 10(-5) M midazolam on [Ca2+]i or tension during the contractions induced by carbachol. CONCLUSIONS: Midazolam directly relaxes airway smooth muscles by decreasing [Ca2+]i; this can be attributed to the inhibition of the influx of extracellular Ca2+. Midazolam has no effect on the release of stored Ca2+. In addition, midazolam has no effect on Ca2+ sensitivity of the contractile apparatus. Finally, benzodiazepine antagonists, flumazenil and PK11195, have no effect on this mechanism of direct action of midazolam on airway smooth muscles. |
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Authors:
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H Yoshimura; T Kai; J Nishimura; S Kobayashi; S Takahashi; H Kanaide |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anesthesiology Volume: 83 ISSN: 0003-3022 ISO Abbreviation: Anesthesiology Publication Date: 1995 Nov |
Date Detail:
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Created Date: 1995-12-21 Completed Date: 1995-12-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1300217 Medline TA: Anesthesiology Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1009-20 Citation Subset: AIM; IM |
Affiliation:
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Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Anxiety Agents / pharmacology* Calcium / metabolism*, pharmacology Drug Interactions Flumazenil / pharmacology Fluorometry GABA Modulators / pharmacology Intracellular Fluid / metabolism Ion Transport Isoquinolines / pharmacology Midazolam / pharmacology* Muscle Contraction / drug effects Muscle, Smooth / drug effects*, metabolism* Potassium / pharmacology Swine Trachea / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Anti-Anxiety Agents; 0/GABA Modulators; 0/Isoquinolines; 59467-70-8/Midazolam; 7440-09-7/Potassium; 7440-70-2/Calcium; 78755-81-4/Flumazenil; 85340-56-3/PK 11195 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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