Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dantrolene sodium, used clinically as a muscle relaxant because of its ability to block Ca2+ efflux from sarcoplasmic reticulum, was used to study the role of intracellular stored Ca2+ in the stimulation of insulin release from rat pancreatic islets. Under basal conditions (2.8 mM glucose), dantrolene (25 microM) decreased 45Ca2+ efflux by 40% without affecting the rate of insulin release. When the islets were exposed to a submaximal stimulatory concentration of glucose (8.3 mM), dantrolene potentiated insulin release. When a supermaximal concentration of glucose (33.3 mM) was used, dantrolene neither increased nor decreased the maximal rate of insulin release. In all cases studied, 45Ca2+ efflux was depressed by dantrolene. 3-Isobutyl-1-methyl-xanthine (IBMX) a phosphodiesterase inhibitor, stimulated insulin release and caused a transient increase in 45Ca2+ efflux from preloaded islets in accord with the idea that it mobilizes Ca2+ from an intracellular store. Dantrolene inhibited IBMX-induced 45Ca2+ efflux and potentiated IBMX-stimulated insulin release. That dantrolene acts to trap calcium in stores is supported by wash-out experiments in which, under basal conditions, removal of the drug after a preincubation period increased both insulin release and 45Ca2+ efflux. The apparent contradiction that a calcium store blocker potentiates insulin release is reconciled by the hypothesis that dantrolene, by filling intracellular Ca2+ stores, causes them to regulate cytosolic Ca2+ at a higher set point.
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PMID:Paradoxical potentiation of stimulated insulin release by dantrolene in rat pancreatic islets. 243 18