Assessment of the muscarinic receptor subtypes involved in pilocarpine-induced seizures in mice

Maslanski, John A.; Powelt, Richard; Deirmengiant, Carl; Patelt, Jitendra

doi:10.1016/0304-3940(94)90456-1

Cited by 30 publications

(19 citation statements)

References 12 publications

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“…The BChE Ϫ/Ϫ mice, but not wild-type mice, had tonicclonic convulsions after treatment with pilocarpine. Pilocarpine induces status epilepticus in rodents by stimulating muscarinic receptors (Maslanski et al, 1994). Our results suggest that muscarinic receptors in the brain of BChE Ϫ/Ϫ mice are hypersensitive to pilocarpine.…”

Section: Discussionmentioning

confidence: 57%

The Butyrylcholinesterase Knockout Mouse as a Model for Human Butyrylcholinesterase Deficiency

Duysen

Carlson

et al. 2007

J Pharmacol Exp Ther

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Section: Discussionmentioning

confidence: 57%

The Butyrylcholinesterase Knockout Mouse as a Model for Human Butyrylcholinesterase Deficiency

Duysen

Carlson

et al. 2007

J Pharmacol Exp Ther

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“…In the forebrain the M1 pharmacological class of mAChR, as defined by pirenzepine antagonism, is linked to phosphatidylinositol turnover (39), the inhibition of the M current (40), and seizure induction by muscarinic agonists (22,23). Because both m1 and m4 subtypes are recovered when [ 3 H]pirenzepinelabeled receptors are immunoprecipitated (28), the involvement of multiple muscarinic receptor subtypes has not been ruled out.…”

Section: Discussionmentioning

confidence: 99%

“…Light microscopy shows damage to several brain regions, including the hippocampus, amygdala, thalamus, olfactory cortex, neocortex, and substantia nigra. Simultaneous injection of the muscarinic antagonists atropine or pirenzepine with pilocarpine prevents the onset of seizures (20), but muscarinic antagonists have no effect on established seizures (21)(22)(23), indicating that mAChRs are involved in the initiation but not the maintenance of epileptic seizures. The m1 and m4 receptor subtypes are both found in the cerebral cortex, hippocampus, and thalamus and have high affinity for pirenzepine (12), so the identity of the mAChR subtype responsible for agonistinduced seizures has been ambiguous.…”

mentioning

confidence: 99%

Disruption of the m1 receptor gene ablates muscarinic receptor-dependent M current regulation and seizure activity in mice

Hamilton

Loose

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

327

267

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Muscarinic acetylcholine receptors are members of the G protein-coupled receptor superfamily expressed in neurons, cardiomyocytes, smooth muscle, and a variety of epithelia. Five subtypes of muscarinic acetylcholine receptors have been discovered by molecular cloning, but their pharmacological similarities and frequent colocalization make it difficult to assign functional roles for individual subtypes in specific neuronal responses. We have used gene targeting by homologous recombination in embryonic stem cells to produce mice lacking the m1 receptor. These mice show no obvious behavioral or histological defects, and the m2, m3, and m4 receptors continue to be expressed in brain with no evidence of compensatory induction. However, the robust suppression of the M-current potassium channel activity evoked by muscarinic agonists in sympathetic ganglion neurons is completely lost in m1 mutant mice. In addition, both homozygous and heterozygous mutant mice are highly resistant to the seizures produced by systemic administration of the muscarinic agonist pilocarpine. Thus, the m1 receptor subtype mediates M current modulation in sympathetic neurons and induction of seizure activity in the pilocarpine model of epilepsy.

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“…By weakening recurrent excitatory circuitry, seizures may not readily become continuous. Another potentially important factor is the decline in muscarinic M1 receptors after ovariectomy (Vaucher et al, 2002), which would limit actions of pilocarpine, because pilocarpine-induced seizures appear to be mediated by M1 receptor activation (Hamilton et al, 1999;Maslanski et al, 1994). Thus, the initial stages of the progression to status may occur rapidly in ovariectomized rats due to disinhibition.…”

Section: Progression To Status Epilepticusmentioning

confidence: 99%

Seizure susceptibility in intact and ovariectomized female rats treated with the convulsant pilocarpine

Scharfman

Goodman

Rigoulot

et al. 2005

Experimental Neurology

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Despite numerous neuroendocrinological studies of seizures, the influence of estrogen and progesterone on seizures and epilepsy remains unclear. This may be due to the fact that previous studies have not systematically compared distinct endocrine conditions and included all relevant controls. The goal of the present study was to conduct such a study using pilocarpine as chemoconvulsant. Thus, age and weight-matched, intact or ovariectomized rats were tested to determine incidence of status epilepticus and to study events leading to status. Intact female rats were sampled at each cycle stage (proestrus, estrus, metestrus, or diestrus 2). Convulsant was administered at the same time of day, 10:00-10:30 a.m. Statistical analysis showed that there was a significantly lower incidence of status on the morning of estrus, but differences were attenuated in older animals. Ovariectomized rats were distinct in their rapid progression to status. These results show that the incidence of status in female rats following pilocarpine injection, and the progression to pilocarpineinduced status, are influenced by reproductive state as well as age. The hormonal milieu present specifically on the morning of estrus appears to decrease susceptibility to pilocarpine-induced status, particularly at young ages. In contrast, the chronic absence of reproductive steroids that characterizes the ovariectomized rat leads to a more rapid progression to status. This dissociation between incidence vs. progression provides new insight into the influence of estrogen and progesterone on seizures.

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Assessment of the muscarinic receptor subtypes involved in pilocarpine-induced seizures in mice

Cited by 30 publications

References 12 publications

The Butyrylcholinesterase Knockout Mouse as a Model for Human Butyrylcholinesterase Deficiency

The Butyrylcholinesterase Knockout Mouse as a Model for Human Butyrylcholinesterase Deficiency

Disruption of the m1 receptor gene ablates muscarinic receptor-dependent M current regulation and seizure activity in mice

Seizure susceptibility in intact and ovariectomized female rats treated with the convulsant pilocarpine

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