title: Synergism between hypotonically induced calcium release and fatty acyl-CoA esters induced calcium release from intracellular stores.
abstract: The non-mitochondrial Ca2+ stores in permeabilized A7r5 cells responded to a decrease in Mg-ATP concentration with a pronounced Ca2+ release if 20 microM CoA was present. This release was rather specific for the preincubation or removal of ATP. ATP gamma S was much less effective and AMP-PNP, GTP, ITP, CTP, UTP, ADP, AMP, adenosine and adenine had no effect. CoA activated with an EC50 of 6 microM. Dephospho-CoA was a less effective cofactor and desulfo-CoA was ineffective. The release induced by Mg-ATP removal did not occur in the presence of 2% fatty acid-free bovine serum albumin and did not develop at 4 degrees C. All these findings suggest that CoA had to be acylated by endogenous fatty-acyl-CoA synthetase to become effective. Myristoyl- and palmitoyl-CoA esters were identified as the most effective cofactors for the release. Ca2+ release induced by removing Mg-ATP did not occur if the osmolality of the medium was kept constant by addition of mannitol, sucrose, KCl, MgCl2 or Mg-GTP, indicating that the decrease in tonicity was the trigger for the release. Mg-ATP plus CoA also synergized with Ca2+ release induced by a hypotonic shock imposed by diluting the medium with H2O. Osmolality changes induced by decreasing the Mg-ATP concentration were more effective in releasing Ca2+ than equal decreases in concentration of all solutes. We conclude that fatty acyl-CoA esters sensitize the hypotonically induced Ca2+ release from the non-mitochondrial Ca2+ stores.
authors.affiliation: Laboratorium voor Fysiologie, KU Leuven Campus Gasthuisberg, Belgium. Ludwig.Missiaen@med.kuleuven.ac.be
authors.forename: L
authors.initials: L
authors.lastname: Missiaen
authors.forename: H
authors.initials: H
authors.lastname: De Smedt
authors.forename: J B
authors.initials: JB
authors.lastname: Parys
authors.forename: H
authors.initials: H
authors.lastname: Sipma
authors.forename: K
authors.initials: K
authors.lastname: Maes
authors.forename: S
authors.initials: S
authors.lastname: Vanlingen
authors.forename: I
authors.initials: I
authors.lastname: Sienaert
authors.forename: W
authors.initials: W
authors.lastname: Van Driessche
authors.forename: R
authors.initials: R
authors.lastname: Casteels
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D007038:Hypotonic Solutions; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009994:Osmolar Concentration; D010171:Palmitoyl Coenzyme A / Q000378:metabolism*; D051381:Rats
chemical_list: D000214:Acyl Coenzyme A; D007038:Hypotonic Solutions; D010171:Palmitoyl Coenzyme A; C040349:S-tetradecanoyl-coenzyme A; D000255:Adenosine Triphosphate; D002118:Calcium