Calmodulin-antagonists inhibit vesicular Ca2+ uptake in Dictyostelium.
Chemotactic stimulation by cAMP elicits Ca2+ entry across the plasma membrane and uptake into intracellular Ca2+ stores. In order to better understand Ca2+ regulation in Dictyostelium we measured 45Ca2+ uptake in homogenates of aggregation competent cells. Besides the InsP3-sensitive store the acidosomes are responsible for Ca2+ transport. About 50% of the vesicular 45Ca2+ accumulation was inhibited by the calmodulin antagonist W-7 and 14% by the less efficacious analogue W-5. Half maximal inhibition by W-7 occurred at 37 microM concentration. Calmodulin antagonised the activity of W-7, and a monoclonal antibody against Dictyostelium calmodulin inhibited Ca2+ sequestration as did calmodulin antagonists of different classes. 100 microM BHQ-a SERCA-type Ca2+ transport ATPase blocker-inhibited most of the W-7 sensitive compartment and oxalate increased Ca2+ uptake into this compartment indicating that intracellular Ca2+ stores are the target of W-7. Ca2+/calmodulin thus seems to provide for a feedback regulation of Ca2+ sequestration.
Gröner
M
M
Fakultät für Biologie, Universität, Germany.
Malchow
D
D
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics*; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004023:Dictyostelium / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
D002147:Calmodulin; D013449:Sulfonamides; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D002118:Calcium