Linked Life Data

8083229

Source:http://linkedlifedata.com/resource/pubmed/id/8083229

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
37
pubmed:dateCreated
1994-10-11
pubmed:abstractText
Macrocyclic natural products derived from bromotyrosine isolated from the sponge Ianthella basta are shown to selectively modulate the skeletal isoform of the ryanodine-sensitive sarcoplasmic reticulum calcium channel by a novel mechanism involving the FKBP12/RyR-1 complex. Bastadins 5, 7, and the newly identified isomer of bastadin 5, bastadin 19, show marked differences in potency and efficacy toward activation of the binding of [3H]ryanodine. In physiological salt, bastadin 5 (5 microM) increases the [3H]ryanodine binding capacity of SR membranes 5-fold, by stabilizing the high affinity conformation of RyR-1 for ryanodine without shifting the affinity of the activator site for Ca2+ or altering the response to caffeine or adenine nucleotides. Bastadin 5 decreases the inhibitory potency of Mg2+ 8-fold and high (> 100 microM) Ca2+ 5-fold. Bastadin 5 inhibits Ca2+ uptake into SR vesicles and enhances Ca(2+)-induced Ca2+ release 8-fold. Bastadin 5 increases single-channel open dwell time, tau 1 and tau 2, 65- and 92-fold, respectively, without changing unitary conductance for Cs+ (450 picosiemans) or open probability. Most significant is the finding that the unique actions of bastadin 5 on [3H]ryanodine binding and Ca2+ transport are antagonized by the immunosuppressant FK506. FK506 alone weakly enhances the binding of [3H]ryanodine, compared to bastadin 5. However, FK506 diminishes bastadin 5-induced changes in [3H]ryanodine binding and Ca2+ transport without altering the efficacy of adenine nucleotides. Unlike FK506, bastadin 5 does not directly promote the dissociation of FKBP12 from the RyR-1 membrane complex; however, it markedly enhances the release of FKBP12 induced by FK506. These results suggest that the bastadin 5 effector site is a novel modulatory domain on FKBP12. Bastadins represent a new class of compounds to gain insight into the functional interactions between FKBP12 and RyR-1.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23236-49
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Novel modulators of skeletal muscle FKBP12/calcium channel complex from Ianthella basta. Role of FKBP12 in channel gating.
pubmed:affiliation
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis 95616.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.