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Inhibition of calcium ATPase by phencyclidine in rat brain (1999)

Pande, M. ; Cameron, J.A. ; Vig, P.J.S. ; [et al.]

Springer

Molecular and cellular biochemistry 194 (1999), S. 173-177

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ISSN: 1573-4919

Keywords: calcium ; ATPase ; central nervous system ; phencyclidine ; inhibition ; in vitro ; in vivo

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Chemistry and Pharmacology , Medicine

Notes: Abstract Phencyclidine (PCP) is a potent psychotomimetic drug of abuse and has profound effect on the functioning of the central nervous system (CNS). Many of the CNS functions are known to be mediated by calcium (Ca2+). In the present study we have investigated the effects of PCP on Ca2+ ATPase activity in rat brain both in vitro and in vivo. For in vitro studies, synaptic membrane fractions prepared from normal rat brain were incubated with PCP at different concentrations (25-100 μM) before the addition of substrate. For n vivo studies, rats were treated with a single moderate dose of PCP (10 mg/kg, IP) and animals were sacrificed at 1,2, 6 and 12 h after treatment. Ca2+ ATPase activity in synaptic membrane fractions was assayed by estimation of inorganic phosphate. PCP inhibited the Ca2+ ATPase in vitro in a concentration dependent manner with significant effect at 50 and 100 μM. A significant time-dependent reduction of the Ca2+ ATPase activity was evident in vivo. As early as 2 h after the treatment of rats with PCP the ATPase activity was significantly reduced. The reduction of Ca2+ ATPase observed even at 12 h after treatment suggesting a prolonged presence of the drug in the brain tissue. Further, kinetic studies in vitro indicated PCP to be a competitive inhibitor of Ca2+ ATPase with respect to the substrate, ATP. The present findings indicate that PCP inhibits synaptic membrane Ca2+ ATPase thus altering cellular Ca2+ homeostasis in CNS which may partially explain the pharmacological effects of the drug and/or its neurotoxicity.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1006911420745

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Inhibition of β-adrenergic stimulated calcium pump of rat cardiac sarcoplasmic reticulum by tricyclohexyltin hydroxide (1987)

Sahib, I. Kabeer Ahammed ; Desaiah, D.

New York, NY [u.a.] : Wiley-Blackwell

Cell Biochemistry and Function 5 (1987), S. 149-154

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ISSN: 0263-6484

Keywords: Plictran ; Ca2+ ATPase ; 45Ca2+ uptake ; inhibition ; sarcoplasmic reticulum ; β-adrenergic stimulation ; Chemistry ; Biochemistry and Biotechnology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Medicine

Notes: The effects of tricyclohexyltin hydroxide (Plictran), an organotin acaricide, on 45Ca2+ uptake and Ca2+ ATPase were studied in vitro and in vivo in rat heart ventricular membrane vesicles, primarily sarcoplasmic reticulum. There was a concentration dependent inhibition of both 45Ca2+ uptake and Ca2+ ATPase in vivo as well as in vitro. Isoproterenol, a β-adrenergic agonist, stimulated 45Ca2+ uptake and Ca2+ ATPase of sarcoplasmic reticulum and this was also inhibited by Plictran. Since cardiac relaxation is mediated by β-adrenergic stimulation via Ca+ uptake by sarcoplasmic reticulum, the inhibition of calcium pump activity by Plictran may result in alterations in cardiac Ca2+ fluxes leading to cardiac dysfunction.

Additional Material: 3 Ill.