Journal article
Tacrolimus (FK506) modulates calcium release and contractility of intestinal smooth muscle
Cell calcium (Edinburgh), Vol.22(6), pp.507-514
12/1997
DOI: 10.1016/S0143-4160(97)90078-6
PMID: 9502200
Abstract
Several proteins have been identified that associate with calcium release channels and potentially regulate their function. Using tacrolimus as a pharmacological tool, we investigated whether the immunophilin FKBP12 modulates ryanodine receptor channels in intestinal smooth muscle. Results with PCR demonstrated the presence of type-3 ryanodine receptor and FKBP12 in this tissue. Tacrolimus caused an irreversible increase of the intracellular calcium concentration, which was abolished by pretreatment with caffeine. The calcium channel blocker verapamil did not affect the response to tacrolimus. Tacrolimus decreased the calcium concentration in the sarcoplasmic reticulum. Caffeine, but not inositol 1,4,5-trisphosphate or heparin, abolished this effect. Finally, tacrolimus significantly and irreversibly decreased the tension generated by intestinal muscle strips. These data support our hypothesis that the immunophilin FKBP12 modulates ryanodine receptor function in smooth muscle. Interactions between such regulatory proteins and calcium release channels may play an important role in excitation-contraction coupling and other intracellular signaling processes.
Details
- Title: Subtitle
- Tacrolimus (FK506) modulates calcium release and contractility of intestinal smooth muscle
- Creators
- Klaus Bielefeldt - Departments of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, USARam V Sharma - Department of Anatomy and Cell Biology, University of Iowa College of Medicine, Iowa City, Iowa, USACarol Whiteis - Departments of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, USAEmre Yedidag - Department of Surgery, University of Iowa College of Medicine, Iowa City, Iowa, USAFrancois M Abboud - Departments of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Cell calcium (Edinburgh), Vol.22(6), pp.507-514
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/S0143-4160(97)90078-6
- PMID
- 9502200
- ISSN
- 0143-4160
- eISSN
- 1532-1991
- Language
- English
- Date published
- 12/1997
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984025675802771
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