Abstract
Several effects of the neuroleptic agent haloperidol on the sarcoplasmic reticulum (SR) Ca-dependent adenosine triphosphatase (Ca-ATPase) and Ca transport are described. Haloperidol inhibits the Ca-ATPase activity in the presence of calcimycin. The effect depends on the conditions of preexposure of the membranes to the drug: the inhibition increases with the preincubation time; Ca and Mg protect the enzyme against the effect of the drug. The inhibitory effect of haloperidol decreases upon increasing [Ca2+], at constant [Mg], and disappears at 20 mM [Mg] for any [Ca2+], and at 0.5 mM [Ca2+] for any [Mg2+]. Haloperidol also inhibits phosphorylation of the enzyme by Pi, and ATP-dependent Ca2+ uptake, in both cases with apparent Ki = 0.10-0.15 mM, and increases the rate of Ca efflux from preloaded vesicles in this concentration range. The results suggest that haloperidol interacts with the catalytic site, interfering with the effect of the divalent catalytic cation, but not at other steps of the enzymatic cycle, where Mg2+ and Ca2+ are also activators. They are consistent with a reaction model where haloperidol interacts with the E2 conformers of the enzyme, with lower affinity for the phosphoenzyme than for the dephospho species. ...Continue Reading
References
Sep 21, 1976·Biochimica Et Biophysica Acta·P J GarrahanG L Alonso
Dec 15, 1979·FEBS Letters·N KolassaM Makinose
Mar 24, 1992·FEBS Letters·L de Meis, G Inesi
Nov 30, 1990·Biochimica Et Biophysica Acta·G L AlonsoD A González
Jun 8, 1989·Nature·D M ClarkeD H MacLennan
Feb 28, 1989·Biochimica Et Biophysica Acta·L de Meis
Jan 1, 1985·Annual Review of Physiology·G Inesi
May 1, 1989·Cell Calcium·J R LópezM J López
Jan 15, 1988·European Journal of Biochemistry·L De MeisA Gómez Puyou
Jan 1, 1986·The Journal of Membrane Biology·J P AndersenP L Jørgensen
Dec 15, 1988·The Biochemical Journal·V Shoshan-Barmatz
Jan 1, 1985·Biochemistry·P ChampeilM P Gingold
Sep 3, 1987·Biochimica Et Biophysica Acta·B Escudero, C Gutiérrez-Merino
May 1, 1994·The American Journal of Physiology·H Wolosker, L de Meis
Jul 6, 1993·Biochemistry·J Reinstein, W P Jencks
Citations
Dec 24, 1997·Annals of the New York Academy of Sciences·D Takara, G L Alonso
Aug 21, 2013·Naunyn-Schmiedeberg's Archives of Pharmacology·G A SánchezD Takara
Jun 21, 2014·Naunyn-Schmiedeberg's Archives of Pharmacology·D E Di CroceD Takara
Jul 16, 2015·Naunyn-Schmiedeberg's Archives of Pharmacology·D Di CroceG A Sánchez
Nov 15, 2013·European Journal of Oral Sciences·Gabriel A SánchezDelia Takara
Oct 24, 1998·Biochimica Et Biophysica Acta·G L AlonsoG A Sánchez
Sep 15, 2012·Archives of Oral Biology·Gabriel Antonio SánchezDelia Takara
Jun 26, 2004·Journal of Dental Research·G A SánchezG L Alonso