Modulation of IP(3)-sensitive Ca(2+) release by 2,3-butanedione monoxime.
We describe the actions of 2,3-butanedione monoxime (BDM) on calcium responses in secretory cells. Our studies were prompted by the widespread use of BDM as a myosin-ATPase inhibitor. Application of 10 mM BDM almost completely inhibited agonist-evoked amylase secretion from mouse pancreatic acinar cells. This action might be interpreted as indicating a role for myosin in secretion. However, BDM alone elicited a calcium response in single cells and this calcium signal was sufficient to activate calcium-dependent chloride currents. Furthermore, in some cases, BDM potentiated agonist-evoked calcium signals but almost always blocked agonist-evoked calcium oscillations. These effects of BDM were not due to an action on calcium influx pathways but rather to direct effects on IP(3)-sensitive stores. We conclude that BDM cannot be used for unequivocal identification of the involvement of myosin motors in a cellular response. Further, our evidence suggests that BDM can act directly to modify the opening of IP(3) receptors.
Turvey
Matthew R
MR
Department of Pharmacology, Tennis Court Road, CB2 1PD, Cambridge, UK. mrt27@cam.ac.uk
Laude
Alex J
AJ
Ives
E Oliver H
EO
Seager
William H
WH
Taylor
Colin W
CW
Thorn
Peter
P
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D021461:Animals, Outbred Strains; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D051379:Mice; D009218:Myosins / Q000037:antagonists & inhibitors; D009991:Oscillometry; D009994:Osmolar Concentration; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques
D004791:Enzyme Inhibitors; C004717:diacetylmonoxime; D015544:Inositol 1,4,5-Trisphosphate; D009218:Myosins; D003931:Diacetyl; D000109:Acetylcholine; D002118:Calcium