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F Fukamauchi

Publications and source records attributed to F Fukamauchi.

31 records · Page 2Linked to original sources
PubMed1995

Halothane prevents MK-801 neurotoxicity in the rat cingulate cortex.

Subcutaneous administration of the N-methyl-D-aspartic acid (NMDA) antagonist, MK-801, to adult rats causes a toxic vacuole reaction in neurons of the posterior cingulate cortex which is readily detected in histological sections 4 h following MK-801 administration. Certain drugs that facilitate neurotransmission at gamma-aminobutyric acidA (GABAA) receptors block this neurotoxic action of MK-801. The anesthetic actions of halothane (fluothane) are thought to be due, at least in part, to an interaction with GABAA receptors. In the present study, we investigated the effect of halothane on MK-801 neurotoxicity. When halothane was administered for either 1 or 2 h, then terminated immediately prior to MK-801 treatment, the vacuole reaction detected 4 h later was almost as severe as in controls not exposed to halothane. Administration of halothane for 1 h after MK-801 injection postponed but did not prevent a relatively full vacuole reaction. However, when rats were kept under halothane anesthesia continuously throughout the 4 h period following MK-801 administration, the vacuole reaction was completely prevented. We postulate that halothane blocks MK-801 neurotoxicity by a facilitative action at GABAA receptors. Because halothane's duration of action is fleeting compared to the very long duration of action of MK-801, the efficacy of halothane in blocking MK-801 neurotoxicity varies in direct proportion to the length of time following MK-801 treatment that the rat brain is exposed to halothane.

Animals↗
PubMed1995

Methamphetamine-induced dopaminergic hyperactivity is not accompanied with increase in tyrosine hydroxylase mRNA of the rat midbrain.

Tyrosine hydroxylase (TH) mRNA was measured in the midbrain of rats treated repeatedly with methamphetamine (MAP). Male Sprague-Dawley rats were daily injected with MAP (5 mg/kg, i.p., once daily) or saline for 14 days. Progressive augmentation was observed in MAP-induced stereotyped behaviors. After one week of abstinence, the rats were decapitated and the brains were prepared for either in situ hybridization using non-radioactive cRNA probes or Northern blot analysis using 32P-labeled cDNA probes. In situ hybridization showed that the signals of TH mRNA were localized to the dopaminergic perikarya in the midbrain and were reduced in MAP-treated animals compared to the controls. Northern blot analysis revealed that the level of TH mRNA in the midbrain of MAP-treated rats was decreased by 37% compared to the controls, which was close to the statistical significance (P = 0.053). These results indicate that the dopaminergic hyperactivity caused by repeated MAP treatment is not associated with enhanced transcription of the TH gene.

Animals↗
PubMed1994

Endothelin-1 increases the levels of mRNA and protein of muscarinic acetylcholine receptors and c-fos mRNA in cerebellar granule cells.

Endothelin-1 (ET-1) induced a time- and dose-dependent increase in the levels of mRNA of m2- and m3-muscarinic acetylcholine receptors (mAChRs) in cultured cerebellar granule cells. The levels of immunoprecipitable m3-mAChR protein and total mAChR binding sites were also increased by ET-1 treatment. The up-regulation of m2- and m3-mAChR was blocked by phorbol ester pretreatment to inhibit ET-1-stimulated phosphoinositide hydrolysis and was preceded by an increase in c-fos mRNA levels. Treatments that prevented ET-1-induced c-fos mRNA increase also abolished the subsequent m2- and m3-mAChR mRNA up-regulation, suggesting that c-Fos protein is involved in the ET-1-induced mAChR expression.

2-Aminopurine↗
PubMed1994

Regulation of beta-adrenergic receptor mRNA in rat C6 glioma cells is sensitive to the state of microtubule assembly.

Microtubule disrupter, colchicine, and microtubule stabilizer, taxol, were used to determine whether microtubules play a role in beta-adrenergic receptor mRNA homeostasis and agonist-induced down-regulation in C6 glioma cells. Colchicine treatment had significant, differential, time-dependent effects on constitutive beta 1- and beta 2-adrenergic receptor mRNA levels. These effects stemmed from the action of colchicine on microtubules, because beta-lumicolchicine, an inactive isomer, had no effect, and nocodazole, a structurally unrelated microtubule disrupter, had similar effects. Colchicine treatment had little effect on the total number of beta-adrenergic receptor binding sites as measured by (-)-[125I]iodopindolol binding, but did alter the relative proportion of beta 1- and beta 2-adrenergic receptor subtypes. Colchicine also had no effect on basal cyclic AMP levels. In contrast to colchicine, taxol treatment had little long-term effect on either beta 1- or beta 2-adrenergic receptor mRNA levels. Taxol antagonized the effects of colchicine on total binding and mRNA levels. Taxol treatment increased basal cyclic AMP levels fourfold and potentiated (-)-isoproterenol-induced cyclic AMP production. Colchicine pretreatment completely inhibited (-)-isoproterenol-induced down-regulation of beta 1-adrenergic receptor mRNA, but not that of beta 2-adrenergic receptor mRNA. Taxol pretreatment had little effect on isoproterenol-induced beta-adrenergic receptor mRNA down-regulation. Colchicine pretreatment also attenuated isoproterenol-induced receptor down-regulation and inhibited agonist-stimulated cyclic AMP production. These effects of colchicine were antagonized by taxol. Whereas the effects of taxol and colchicine on isoproterenol-induced down-regulation of beta-adrenergic receptor mRNA are consistent with their effects on cyclic AMP production, those of colchicine in the absence of stimulation must involve other mechanisms. The data demonstrate that the state of microtubule assembly can affect cyclic AMP levels, beta 1- and beta 2-adrenergic receptor mRNA, and binding site levels in C6 glioma cells.

Animals↗
PubMed1993

Long-term biphasic effects of lithium treatment on phospholipase C-coupled M3-muscarinic acetylcholine receptors in cultured cerebellar granule cells.

We have studied the long-term effects of lithium on neuronal morphology and the functional expression of phospholipase C-coupled m3-muscarinic acetylcholine receptors (mAChRs) in cerebellar granule cells. There was a biphasic dose-dependent effect on cell morphology following treatment with lithium for 7 days. At low concentrations (< or = 2 mM), this drug elicited an increase in the number and thickness of connecting nerve fibers, and the size of neuronal aggregates. At high concentrations (5-10 mM), lithium induced a severe deterioration of cell morphology, which ultimately resulted in neuronal death. Carbachol-induced phosphoinositide (PI) turnover was similarly affected by lithium treatment with a significant potentiation at concentrations up to 2 mM and a marked inhibition at doses higher than 5 mM due to lithium-induced neurotoxicity. The biphasic effect on mAChR-mediated PI hydrolysis was associated with corresponding changes in the maximal extent of carbachol-induced inositol phosphate accumulation, and was accompanied by similar changes in [3H]N-methyl-scopolamine binding to mAChRs and the levels of mRNAs for m3-mAChR and c-Fos. The up-regulation of m3-mAChR mRNA induced by low concentrations of lithium was associated with a down-regulation of m2-mAChR mRNA and no change in either total RNA or beta-actin mRNA. Lithium's effects on m2- and m3-mAChR mRNAs were time-dependent, requiring a pretreatment time of > or = 3 days. The biphasic effect was also demonstrated by the binding of [3H]ouabain to Na+, K(+)-ATPase, which was shown to be a convenient method for quantifying viable neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Agonist-induced down-regulation and antagonist-induced up-regulation of m2- and m3-muscarinic acetylcholine receptor mRNA and protein in cultured cerebellar granule cells.

Cerebellar granule cells express m2- and m3-muscarinic acetylcholine receptors (mAChRs) and their corresponding mRNA with m3-mAChR being the predominant receptor subtype. After stimulation with the mAChR agonist, carbachol, m2- and m3-mAChR mRNA levels were decreased in a time- and concentration-dependent manner with the maximal down-regulation at 2 and 8 hr, respectively. Immunoprecipitation studies revealed that amounts of m2- and m3-mAChR protein also decreased at 8 and 24 hr, respectively. The carbachol-induced down-regulation of m3-mAChR mRNA was associated with a decrease in the transcription rate, but a substantial enhancement of the mRNA stability. Upon removal of carbachol after treatment for 8 hr, the levels of m3-mAChR mRNA and mAChR binding sites returned to their original values with a t1/2 of approximately 80 min and 6 hr, respectively. The carbachol-elicited loss of m2- and m3-mAChR mRNA was blocked by their corresponding receptor subtype-specific antagonists, AF-DX 116 (m2-selective) and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) (m3-selective), and was concurrent with an increase in c-fos mRNA levels. Exposure of granule cells to the nonselective mAChR antagonist, atropine, caused a time- and concentration-dependent increase in the level of both m2- and m3-mAChR mRNA and mAChR binding sites. At 24 hr, immunoprecipitable m3-mAChR protein was predominantly increased. The atropine-induced up-regulation of m3-mAChR mRNA was concurrent with a marked enhancement of the mRNA stability and its transcription rate. The elevated levels of m3-mAChR mRNA and binding sites declined to their untreated values after the removal of atropine. Treatment with AF-DX 116 and 4-DAMP also produced an increase in the level of m2- and m3-mAChR mRNA and their corresponding immunoprecipitable receptor protein. These results demonstrate that the mAChR agonist and antagonist induce a down- and up-regulation of mAChR expression, respectively, through receptor-mediated mechanisms in cerebellar granule cells. Moreover, at least for m3-mAChR mRNA, the agonist- and antagonist-induced effects are reversible and associated with corresponding changes in the transcription rate of this receptor mRNA species.

Animals↗
PubMed1992

Pre-synaptic dopaminergic control mechanisms for CCK-8 like immunoreactivity in the rat medial frontal cortex.

In order to study the control mechanism of cholecystokinin (CCK) contents of the rat brain mediated by pre-synaptic receptors in dopamine (DA) neurons, R(+) and S(-) compounds of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP), which are selective pre-synaptic dopaminergic agents, were administered in rats at low and high doses. CCK-8-like immunoreactivity (CCK-8 LI) was measured in the medial frontal cortex. In another experiment, a neurotoxin, N-methyl-D-aspartic acid (NMDA) was used to degenerate efferent CCK neurons and CCK interneurons of the medial frontal cortex, followed by an intraperitoneal administration of apomorphine hydrochloride (APO) to study the effect on CCK-8 LI via the pre-synaptic DA receptor. According to the results of these experiments, CCK-8 LI was increased in the medial frontal cortex in response to the stimulation of pre-synaptic DA receptor, suggesting a control of CCK-8 release, at least in part, by the pre-synaptic DA receptor.

Animals↗
PubMed1991

Expression and agonist-induced down-regulation of mRNAs of m2- and m3-muscarinic acetylcholine receptors in cultured cerebellar granule cells.

The regulation and expression of muscarinic acetylcholine receptor (mAChR) mRNA was studied in cultured cerebellar granule cells using Northern blot hybridization, mRNA species for m2- and m3-mAChRs but not m1- and m4-mAChRs were detected in these cells. The expression of mRNAs of both m2- and m3-mAChRs reached a maximum on the tenth day in culture but their expression patterns differed. Treatment of cerebellar granule cells after 8 days in culture with 100 microM carbachol led to differential down-regulation of the mRNA species of both mAChR subtypes present. Muscarinic receptor antagonists, atropine (1 microM) and pirenzepine (10 microM), prevented carbachol-induced m3-mAChR mRNA down-regulation observed at 8 h. However, exposure to either atropine or pirenzepine alone for 8 h led to a significant up-regulation of m3-mAChR mRNA. Thus, the mRNA species for both m2- and m3-mAChR subtypes are differentially expressed in culture and down-regulated by agonist stimulation. The loss of these mRNA species may play a role in the down-regulation of mAChR binding sites that occurs after desensitization.

Animals↗
PubMed1987

Dopaminergic agents affected neuronal transmission of cholecystokinin in the rat brain.

In order to study the interaction between cholecystokinin (CCK) and dopamine (DA), we prepared an anti-CCK-8 antibody with low cross reactivity, and observed effects of administered various dopaminergic agents on CCK-immunoreactivity (CCK-IR) in discrete brain regions of rats. CCK-8 IR (boiling water extraction) and CCK-33 IR (acetic acid extraction) were also measured in the same sample. A single administration of haloperidol decreased the CCK-8 IR in the corpus striatum and that of racemic sulpiride significantly decreased the CCK-8 IR in the frontal cortex and the limbic system. In contrast, a single administration of apomorphine or methamphetamine increased the CCK-8 IR in the same regions. These findings suggest that an acute response of the CCK system to administered dopaminergic agents may be due to a change in the rate of release of CCK-8, but not to a change in its synthesis in areas in which DA neurons originating in the midbrain innervate. After chronic administration of racemic sulpiride or methaphetamine, CCK-8 IR in various brain regions exhibited a tendency close to that of control.

Animals↗
PubMed1987

The chronic administration of dopamine antagonists and methamphetamine changed the [3H]-cholecystokinin-8 binding sites in the rat frontal cortex.

The specific cholecystokinin (CCK) binding in the slide-mounted tissue sections of the rat frontal cortex was measured with [3H]-CCK-8. The binding was saturable, reversible, high in affinity, and inhibited by caerulein. The chronic administration of dopamine (DA) antagonists and methamphetamine (MAP) showed a tendency to increase the [3H]-CCK-8 binding sites (Bmax) in the frontal cortex. Long-term treatments with DA antagonists led to the depletion of CCK-8 and may have caused an observed proliferation of CCK-8 receptors in the frontal cortex.

Animals↗
PubMedDate not supplied

Regional effects of apomorphine on rat brain cholecystokinin-8 like immunoreactivity following electrolytic lesions of the ventral tegmental area.

After bilateral electrocoagulation of the ventral tegmental area (VTA) of rats, apomorphine (APO) was administered intraperitoneally to study the effect on the cholecystokinin-8 like immunoreactivity (CCK-8 IR) in the medial prefrontal cortex, the anterior and posterior part of the nucleus accumbens and the corpus striatum. In the medial prefrontal cortex and the posterior part of the nucleus accumbens, CCK-8 IR was markedly decreased by lesioning of the VTA. Then recovery of CCK-8 IR was noted in the APO treated rats following electrolytic lesioning of the VTA. This recovery corresponds to the response of CCK neurons not originating in the VTA or CCK interneurons to APO via DA receptors. In the anterior part of the nucleus accumbens and the corpus striatum, no significant decrease in CCK-8 IR was noted even following lesioning of the VTA. APO administration following the lesioning, however, resulted in a marked increase in CCK-8 IR in the anterior part of the nucleus accumbens and the corpus striatum. According to this result, in these sites, very few CCK neurons originating in the VTA exist and CCK neurons originating in sites other than the VTA or CCK interneurons react on APO via DA receptors.

Animals↗
PubMedDate not supplied

Apomorphine affects cholecystokinin content via preferentially D1 or D2 dopamine receptor according to the regions of the rat brain.

Cholecystokinin octapeptide-like immunoreactivity (CCK-8IR) was measured in several regions of the rat brain after the intraperitoneal administration of apomorphine, SKF-38393 (D1 agonist), LY-171555 (D2 agonist). In the medial prefrontal cortex and striatum, apomorphine and SKF 3839 decreased CCK-8IR. In the anterior and posterior nucleus accumbens, on the other hand, the inhibitory effect of apomorphine was mimicked by LY-171555. These results suggest that apomorphine affects CCK-8IR via either the D1 dopamine (DA)-receptor or D2 DA-receptor according to the brain region.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗