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.
journal_name
Cell Calciumjournal_title
Cell calciumauthors
Bielefeldt K,Sharma RV,Whiteis C,Yedidag E,Abboud FMdoi
10.1016/s0143-4160(97)90078-6subject
Has Abstractpub_date
1997-12-01 00:00:00pages
507-14issue
6eissn
0143-4160issn
1532-1991pii
S0143-4160(97)90078-6journal_volume
22pub_type
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