Effect of age, sex steroids, brain region, and genetic strain on brain inositol monophosphatase activity
1996; Elsevier BV; Volume: 40; Issue: 7 Linguagem: Inglês
10.1016/0006-3223(96)00267-3
ISSN1873-2402
AutoresYardena Patishi, Robert H. Belmaker, Galila Agam,
Tópico(s)Bipolar Disorder and Treatment
ResumoInositol monophosphatase (I-M-P'ase), .which catabolizes inositol monophosphate to inositol (Hallcher and Sherman 1980), is a key enzyme in the phosphatidylinositol (PI) cycle that serves as a second messenger system for several brain neurotransmitters (Belmaker et al 1990). Inhibition of inositol monophosphatase by Li (Ki = 0.86 mmol/L) (Moscovich et al 1990) reduces inositol levels by up to 30% (Sherman et ai 1985; Sherman et al 1987). Inositol reduction has been shown to be physiologically important, since replacement by exogenous inositol has been shown to reverse Li's effects in several systems, such as Li-pilocarpine seizures in rats (Kofman et al 1992). Li has powerful therapeutic and prophylactic effects on both phases of bipolar manicdepressive illness (Belmaker 1981). Berridge (1989) proposed that Li's reduction of inositol levels would lead to reduced resynthesis of phosphatidylinositol only in overactive systems, thus leading to their effective dampening. The mechanism of Li's inhibition of inositol monophosphatase is uncompetitive (Nahorski et al 1991). Thus, increasing substrate concentrations to compensate for Li's reduction of the rate of inositol monophosphatase catabolism is particularly ineffective, since elevated substrate concentrations potentiates the inhibition; however, inositol formation will be directly propor-
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