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Modulation of the Ca2+ pump by the hypothalamic-hypophysary inhibitory factor
M Ricote1, E García-Martín, J Sancho
1Serv. Endocrinología, Hospital Ramón y Cajal, Madrid, Spain.
Hypertension (Dallas, Tex. : 1979)
|March 1, 1995
Summary
Researchers identified a novel endogenous inhibitor affecting the calcium pump and Mg(2+)-ATPase activity in synaptosomes. This factor may regulate calcium homeostasis by disrupting the lipid annulus, potentially increasing cytosolic free calcium.
Area of Science:
- Biochemistry
- Neuroscience
- Cell Biology
Background:
- An endogenous sodium pump inhibitor was previously isolated from bovine hypothalamus and hypophysis.
- This inhibitor is distinct from known cardiac glycosides like digoxin and ouabain.
- Its effects on synaptosomal plasma membrane Ca2+,Mg(2+)-ATPase activity were investigated.
Purpose of the Study:
- To characterize the inhibitory effects of the endogenous factor on Ca2+,Mg(2+)-ATPase activity in synaptosomes.
- To elucidate the mechanism of inhibition and its potential role in calcium homeostasis.
Main Methods:
- Purification of the endogenous inhibitor.
- Enzymatic assays measuring Ca2+,Mg(2+)-ATPase activity in synaptosomal plasma membranes.
- Kinetic analysis of inhibition (K0.5 values, noncompetitive inhibition with respect to Mg(2+)-ATP).
Main Results:
- The endogenous factor inhibits both the calcium pump and total Mg(2+)-ATPase activity with similar K0.5 values.
- Inhibitor potency is dependent on membrane concentration.
- Inhibition is noncompetitive with respect to Mg(2+)-ATP and does not alter calcium dependence.
Conclusions:
- The endogenous inhibitor likely disrupts the lipid annulus surrounding the calcium pump.
- This disruption leads to inhibition of the calcium pump in synaptosomal plasma membranes.
- This mechanism may contribute to the regulation of calcium homeostasis by increasing cytosolic free calcium.