Inhibition of agonist‐stimulated inositol lipid metabolism by the anticonvulsant carbamazepine in rat hippocampus

McDermott, E. E.; Logan, S.D.

doi:10.1111/j.1476-5381.1989.tb12632.x

Cited by 8 publications

(4 citation statements)

References 45 publications

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“…CBZ iru'libits the accumulation of cyclic AMP in brain slices stimulai.ed by noradrena· line, ouabain and adenosine (Lewin and Bleck, 1977;Palmer et al, 1979;Skerritt et al, 1983a;Weir et al, 1984), although only at high concentrations. CBZ's effects on the agonist-evoked formation of inositol phos-289 phates are controversial (Elphick et al, 1988: MeDermatt andLogan, 1989).…”

Section: Discussionmentioning

confidence: 99%

Carbamazepine distinguishes between adenosine receptors that mediate different second messenger responses

Calker¹,

Steber²,

Klotz

et al. 1991

European Journal of Pharmacology: Molecular Pharmacology

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The mechanism of the therapeutic and prophylactic effects of carbamazepine (CBZ) in affective psychose.s is unknown but may in part be related to the potent competitive interaction of CBZ with adenosine-binding sites in the brain. The antioonvuls4l:At and sedative properties of CBZ are reminiscent of the effects evoked by adenosine-agonists and contrast sharply with the opposite aclions of adenosine-antagonists like caffeine. However. indirect evidence suggests an antagonist-rather than an agonist-like activity of CBZ at adenosi11e-receptors. We have used various model systems, in which adenosine receptor subtypes mediate different second messenger-responses, to investigate this apparent paradox. CBZ was found to antagonize the Ai·ret:eptor-mediated inhibition of cydic AMP accumulation in cultured astroblasts and in GH 3 -cells. Furthermore, CBZ also inh.ibits the adenosi.ne-induced increase in the Ievel of cyclic ".MP in cultured astrobla.sts, which is med.iated by low-affinity A 2 b-receptors. ln contrast, CBZ does not block the inhibition elicited by adenosine-agonists of the agonist-induced increased formation of inositolphosphates in human neutrophils, which is mediated by high-affinity A 23 -receptors. The specific antagonism by CBZ of A 1 -but not of high-affinity A 23 -receptors was further supported by binding experiments using rat brain membranes. These results suggest tbat the paradox of CBZ's antagonistic effects at adenosine-receptors might be at least partially reconciled by a selective anta%onistic action of CBZ at A 1 recertors but not at high-affinity A2a-receptors.

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Section: Discussionmentioning

confidence: 99%

Carbamazepine distinguishes between adenosine receptors that mediate different second messenger responses

Calker¹,

Steber²,

Klotz

et al. 1991

European Journal of Pharmacology: Molecular Pharmacology

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“…Furthermore, earlier attempts to identify carbamazepine-induced alterations of phosphoinositol signaling have lead to equivocal results (McDermott and Logan 1989;Elphick et al 1988). It may, therefore, be surprising that carba-mazepine evokes effects on inositol uptake, which follow a time course somewhat similar to that of the actions of lithium and valproate, with the exception of the initial decrease in activity in astrocytoma cells, which is not observed with carbamazepine (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the High Affinity Myo-Inositol Transport System A Common Mechanism of Action of Antibipolar Drugs?

Lubrich

Calker

1999

Neuropsychopharmacology

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Manic-depressive disorder is an at least in part genetically transmitted illness that affects one to two percent of the population and is characterized by episodic mood swings in the form of depressive, and manic episodes (Goodwin and Jamison 1990). It can be effectively treated acutely and prophylactically by antibipolar drugs like lithium salts, carbamazepine and valproate. Recent evidence indicates that lithium's beneficial effects might be related to a modulation of cellular signal transducing mechanisms (for review see Berridge et al. 1989;Jope and Williams 1994). In particular, the "inositol depletion" hypothesis (Berridge et al. 1989) conjectures that lithium might act via depletion of susceptible brain areas of myo-inositol, which is necessary to form inositolphospholipids, an integral part of the cell membrane. The breakdown of these lipids by receptor-triggered activation of phospholipase C leads to the formation of the two second messenger molecules, inositol-1,4,5-trisphosphate and diacylglycerol (DAG), which regulate many cellular activities. The lithium induced decrease of the cellular inositol content is postulated to selectively impair pathological overactivation of this system via insufficient supply of inositol for the resynthesis of inositolphospholipid or perhaps other mechanisms secondary to inositol depletion such as activation of protein kinase C (PKC) by accumulated DAG (Jope and Williams 1994). The reason for lithium's inositol depleting effect and for its selectivity for overactivated neural circuits is believed to be the inhibition of inositolmonophosphatase (IMPase), which is of the uncompetitive type and therefore the more pronounced the more substrate (inositolmonophosphate, IMP) is formed by breakdown of inositolphospholipids. The inositol depletion hypothesis rests

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“…Under the conditions used here, the combination of pilocarpine and lithium treatments had a muscarinic receptor-mediated proconvulsive effect and it is pertinent to ask whether the changes in phosphoinositide were the cause or effect of this action. Kindling has been reported to enhance excitatory amino acid-stimulated phosphoinositide hydro~lysis (ladorinoaet al, R1986), sokativation of this transduction system does seem to be involved in the development of seizures and the anticonvulsant carbamazepine (McDermott & Logan, 1989) reduces basal and muscarinic receptor-stimulated [3H]-Ins P's accumulation, again suggesting that products of phosphoinositide hydrolysis have a causal role in seizure production, rather than being a response to the condition.…”

Section: Recent In Vitro Studies Have Shown That Lithium Reducesmentioning

confidence: 99%

The effects of acute and chronic lithium treatment on pilocarpine‐stimulated phosphoinositide hydrolysis in mouse brain in vivo

Whitworth

Heal²,

Kendall

1990

British J Pharmacology

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Inhibition of agonist‐stimulated inositol lipid metabolism by the anticonvulsant carbamazepine in rat hippocampus

Cited by 8 publications

References 45 publications

Carbamazepine distinguishes between adenosine receptors that mediate different second messenger responses

Carbamazepine distinguishes between adenosine receptors that mediate different second messenger responses

Inhibition of the High Affinity Myo-Inositol Transport System A Common Mechanism of Action of Antibipolar Drugs?

The effects of acute and chronic lithium treatment on pilocarpine‐stimulated phosphoinositide hydrolysis in mouse brain in vivo

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