Biomedical subjects

A M Lin

Publications and source records attributed to A M Lin.

At least 19 recordsLinked to original sources

PubMed2001

Coexistence of zinc and iron augmented oxidative injuries in the nigrostriatal dopaminergic system of SD rats.

Clinical studies have demonstrated an excess of transition metals, including zinc and iron, in the substantia nigra (SN) of Parkinson's patients. In the present study, the neurotoxic effect of zinc was investigated using iron as a positive control. Addition of zinc or iron to brain homogenates increased lipid peroxidation. Zinc was less potent than iron in inducing lipid peroxidation. Coincubation with desferrioxamine prevented zinc- and iron-induced lipid peroxidation. Furthermore, glutathione (GSH), S-nitroso-N-acetylpenicillamine, or melatonin inhibited zinc-induced lipid peroxidation. The oxidative effect of zinc was further investigated in anesthetized rats. Seven days after intranigral infusion of zinc, lipid peroxidation was elevated in the infused SN, and dopamine content and tyrosine hydroxylase-positive axons were decreased in the ipsilateral striatum. Zinc was less potent than iron in inducing neurodegeneration in vivo. L-Buthionine-[S,R]-sulfoximine pretreatment (i.c.v.), which depletes cellular GSH levels, enhanced zinc-induced oxidative injuries in the nigrostriatal dopaminergic system. Moreover, simultaneous infusion of zinc and iron appeared to augment oxidative injuries in rat brain. Taken together, our results demonstrate that intranigral infusion of zinc caused degeneration of the nigrostriatal dopaminergic system in rat brain. Furthermore, coexistence of zinc and iron augmented oxidative injuries in rat brain. These findings indicate that both zinc and iron contribute to the etiology of Parkinsonism.

Anesthesia↗

PubMed2001

Optimization of culture conditions to enhance transfection of human CD34+ cells by electroporation.

The ability to culture CD34+ stem cells, while maintaining their pluripotency, is essential for manipulations such as gene transfection for therapeutic trials. Human peripheral blood (PB) CD34+ cells (> or = 90% purity) were cultured for up to 4 days in serum-free culture medium supplemented with thrombopoietin (TPO), stem cell factor (SCF), Flt-3 ligand (Flt-3L), with or without PIXY321 (IL-3/GM-CSF fusion protein) and human serum. The CD34 mean fluorescence intensity (MFI) and cell cycle status were evaluated daily using flow cytometry and hypotonic propidium iodide. Prior to culture (day 0), 97.0 +/- 0.9%, 1.9 +/- 0.3% and 1.0 +/- 0.6% of the selected CD34+ cells were in G0-G1, S-phase, or G2-M, respectively. After 2-4 days in culture with TPO/SCF/Flt-3L, there was an increase in the percent of cells in S-phase to 26.4 +/- 0.1% without significant loss of CD34 MFI. The addition of PIXY321 increased.the percentage of CD34+ cells in S-phase to 36.3 +/- 4.0%, but the CD34 MFI and numbers of CFU (colony-forming units) were significantly decreased at day 3 when cultured with PIXY321 or various recombinant cytokine combinations that included IL-3 and IL-6. There is an increase from day 0 to day 4 in the percentages of CD34+ with CD38-, HLA-DR-, and c-kit(low), but not Thy-1+ cells. Electroporation with EGFP reporter gene showed that 1-2 days of pre-stimulation in X-VIVO 10 supplemented with TPO/SCF/Flt-3L was necessary and sufficient for efficient transfection. Flow cytometry analysis demonstrated that 22% of the viable cells are CD34+/EGFP+ 48 h post electroporation. The introduced reporter gene appears to be stable as determined by EGFP+/LTC-IC (long-term colony-initiating cells), at 30-40 positive colonies (16 +/- 7%) per 1 x 10(5) electroporated CD34+ cells.

Antigens, CD34↗

PubMed2001

Lack of protective effect by intermittent hypoxia on MPTP-induced neurotoxicity in mice.

In the study we report here, several lines of evidence support the preventive action of intermittent hypoxia against oxidative injuries in CNS. Our in vitro data showed that autooxidation and iron-induced lipid peroxidation were attenuated in cortical homogenates of intermittent hypoxia-treated animals. Furthermore, our preliminary study found that iron induced oxidative injuries were abolished in rat brain after intermittent hypoxic treatment (paper submitted). Several antioxidative defensive systems improve in response to intermittent hypoxia. Since attenuation of autooxidation and iron-induced lipid peroxidation were observed in cortical homogenates of intermittent hypoxia-treated mice, the lack of prevention by intermittent hypoxia of MPTP-induced neurotoxicity may be due to the MPTP action that is not oxidative related. Together with our previous studies, in which several antioxidants were shown to successfully prevent oxidative injuries, our data here suggest that intermittent hypoxia may offer a potential treatment for preventing CNS degenerative diseases.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2000

Melatonin suppresses iron-induced neurodegeneration in rat brain.

The antioxidative action of melatonin on iron-induced neurodegeneration in the nigrostriatal dopaminergic system was evaluated in vivo. Intranigral infusion of iron chronically degenerated the dopaminergic transmission of the nigrostriatal system. An increase in lipid peroxidation in the infused substantia nigra and reductions in dopamine levels and dopaminergic terminals in the ipsilateral striatum were observed 7 d after iron infusion. Whereas local infusion of melatonin (60 microg/microl, 1 microl) alone did not alter dopaminergic transmission, coinfusion of melatonin with iron suppressed iron-induced oxidative damages. Systemic infusion of melatonin via osmotic pumps had no effect on iron-induced neurodegeneration. However, repetitive intraperitoneal injections of melatonin (10 mg/kg) prevented iron-induced oxidative injuries. The ratio of glutathione (GSH)/oxidized glutathione (GSSG) was moderately increased in the lesioned substantia nigra of the melatonin-treated rats compared to that of the lesioned group in control rats. The antioxidative effect of melatonin was verified in cortical homogenates. Melatonin dose-dependently suppressed autoxidation and iron-induced lipid peroxidation. Melatonin was as effective as GSH and was less effective than Trolox (a water-soluble analogue of vitamin E) in inhibiting iron-elevated lipid peroxidation of brain homogenates. Our data suggest that melatonin is capable of at least partially preventing the iron-induced neurodegeneration in the nigrostriatal dopaminergic system.

Animals↗

PubMed1999

Recovery by NO of the iron-attenuated dopamine dynamics in nigrostriatal system of rat brain.

In vivo electrochemical detection was employed to study the chronic effect of nitric oxide on iron-induced alterations in dopamine dynamics, including K+ -evoked dopamine overflows and the clearance of exogenous dopamine in rat striatum. Intranigral infusion of fresh S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide donor, did not alter either dopamine dynamics in the striatum or the lipid peroxidation in substantia nigra 7 days after the infusion, indicating that nitric oxide is not neurodestructive. By contrast, infusion of iron in substantia nigra chronically degenerated the nigrostriatal dopaminergic system. Co-infusion of iron and fresh SNAP, but not aged SNAP, prevented the iron-induced reductions in K+ -evoked dopamine overflows. Furthermore, the clearance of exogenous dopamine was attenuated in the striatum ipsilateral to the substantia nigra infused with iron. An improvement by fresh SNAP of iron-induced reduction in dopamine clearance was observed in rats co-infused with fresh SNAP and iron mixture compared to iron-lesioned group. Taken together, our in vivo electrochemical study suggests that nitric oxide does not alter dopamine dynamics in nigrostriatal dopaminergic system. Rather, nitric oxide appears to protect dopamine dynamics from iron-induced oxidative stress in rat brain.

Animals↗

PubMed1999

Carboxyfullerene prevents iron-induced oxidative stress in rat brain.

Carboxyfullerene, a water-soluble carboxylic acid derivative of a fullerene, was investigated as a protective agent against iron-induced oxidative stress in the nigrostriatal dopaminergic system of anesthetized rats. Intranigral infusion of exclusive carboxyfullerene did not increase lipid peroxidation in substantia nigra or deplete dopamine content in striatum. Infusion of ferrous citrate (iron II) induced degeneration of the nigrostriatal dopaminergic system. An increase in lipid peroxidation in substantia nigra as well as decreases in K+-evoked dopamine overflow and dopamine content in striatum were observed 7 days after the infusion. Co-infusion of carboxyfullerene prevented iron-induced oxidative injury. Furthermore, tyrosine hydroxylase-immunoreactive staining showed that carboxyfullerene inhibited the iron-induced loss of the dopaminergic nerve terminals in striatum. The antioxidative action of carboxyfullerene was verified by in vitro studies. Incubation of brain homogenates increased the formation of the Schiff base fluorescent products of malonaldehyde, an indicator of lipid peroxidation. Both autooxidation (without exogenous iron) and iron-induced elevation of lipid peroxidation of brain homogenates were suppressed by carboxyfullerene in a dose-dependent manner. Our results suggest that intranigral infusion of carboxyfullerene appears to be nontoxic to the nigrostriatal dopaminergic system. Furthermore, the potent antioxidative action of carboxyfullerene protects the nigrostriatal dopaminergic system from iron-induced oxidative injury.

Animals↗

PubMed1999

The antioxidative effect of carboxyfullerenes (C3/D3) on iron-induced oxidative injury in CNS.

Carboxyfullerenes, including two regioisomers C3 and D3, were investigated as antioxidants against iron-induced oxidative stress in vivo and in vitro. Both C3 and D3 dose-dependently inhibited autoxidation and iron-elevated lipid peroxidation in cortical homogenates. The antioxidative property of C3 was compared to Trolox (a water-soluble analogue of vitamin E) and glutathione. C3 was more effective than glutathione but was less effective than Trolox in inhibiting iron-induced elevation in lipid peroxidation. In urethane-anesthetized rats, intranigral infusion of iron degenerated the nigrostriatal dopaminergic system, including as elevation in lipid peroxidation in the infused substantia nigra (SN) and reductions in K(+)-evoked dopamine overflow and dopamine content in the ipsilateral striatum 7 days after the infusion. Local application of iron with C3 or D3 prevented iron-induced oxidative injuries. Our data suggest that carboxyfullerenes have a neuroprotective effect in preventing iron-induced oxidative injury in CNS.

Animals↗

PubMed1998

The antioxidative property of green tea against iron-induced oxidative stress in rat brain.

The antioxidative property of green tea against iron-induced oxidative stress was investigated in the rat brain both in vivo and in vivo. Incubation of brain homogenates at 37 degrees C for 4 hours in vitro increased the formation of Schiff base fluorescent products of malonaldehyde, an indicator of lipid peroxidation. Auto-oxidation (without exogenous iron) of brain homogenates was inhibited by green tea extract in a concentration-dependent manner. Moreover, incubation with iron (1 microM) elevated lipid peroxidation of brain homogenates after 4-hour incubation at 37 degrees C. Co-incubation with green tea extract dose-dependently inhibited the iron-induced elevation in lipid peroxidation. For the in vivo studies: ferrous citrate (iron, 4.2 nmoles) was infused intranigrally and induced degeneration of the nigrostriatal dopaminergic system of rat brain. An increase in lipid peroxidation in substantia nigra as well as a decrease in dopamine content in striatum was observed seven days after the iron infusion. Intranigral infusion of green tea extract alone did not increase, and in some cases, even decreased lipid peroxidation in substantia nigra. Co-infusion of green tea extract prevented oxidative injury induced by iron. Both iron-induced elevation in lipid peroxidation in substantia nigra and iron-induced decrease in dopamine content in striatum were suppressed. Oral administration of green tea extract for two weeks did not prevent the iron-induced oxidative injury in nigrostriatal dopaminergic system. Our results suggest that intranigral infusion of green tea extract appears to be nontoxic to the nigrostriatal dopaminergic system. Furthermore, the potent antioxidative action of green tea extract protects the nigrostriatal dopaminergic system from the iron-induced oxidative injury.

Administration, Oral↗

PubMed1998

Role of dopamine uptake in NMDA-modulated K(+)-evoked dopamine overflow in rat striatum: an in vivo electrochemical study.

An involvement of dopamine uptake in the N-methyl-D-aspartate (NMDA)-modulated dopaminergic transmission in rat striatum was studied using the technique of in vivo electrochemical detection. Microinjection of potassium (K+) evoked dopamine overflows from the dopamine-containing nerve terminals in the striatum. While application of NMDA did not evoke any dopamine overflow, co-application of NMDA and K+ induced larger dopamine overflows than those by K+ alone. Furthermore, dynamic analysis showed that the rate of clearance (Tc) was reduced by NMDA. Indeed, our uptake study demonstrated an NMDA-induced inhibition of dopamine clearance. The time course of electrochemical signals evoked by microinjection of exogenous dopamine was increased and Tc was reduced following NMDA application. In order to delineate the effects of NMDA on K(+)-evoked dopamine overflows and/or on dopamine uptake, nomifensine, a dopamine uptake inhibitor was used. Application of nomifensine potentiated K(+)-evoked dopamine overflows. Co-administration of NMDA further augmented dopamine overflows by the K+ and nomifensine mixture. Taken together, our data suggest that NMDA concomitantly potentiated dopamine overflows in response to depolarizing stimuli and attenuated dopamine uptake. The increment by NMDA of K(+)-evoked dopamine overflows may partially result from an attenuated dopamine uptake in rat striatum.

Animals↗

PubMed1998

Striatal dopamine dynamics are altered following an intranigral infusion of iron in adult rats.

In vivo electrochemical detection was employed to examine iron-induced oxidative injury on dopamine dynamics in the nigrostriatal system of urethane-anesthetized rats. Seven days after an intranigral infusion of iron, oxidative stress was confirmed by an elevated lipid peroxidation in lesioned substantia nigra (SN). Local application of potassium (K+) evoked dopamine releases from the dopamine-containing nerve terminals in the striatum. Both amplitude and rate of clearance (Tc) of evoked dopamine releases were lower in striatum with lesioned SN; however, the time course parameters of dopamine release in the lesioned group were not different from those of the intact group, indicating a reduction in dopamine clearance. Indeed, iron-induced oxidative stress attenuated the effect of nomifensine, a high-affinity dopamine uptake blocker, on dopamine clearance. In striatum with intact SN, the amplitude and time course parameters of signals by exogenous dopamine were increased and Tc was decreased by nomifensine. In contrast, nomifensine did not significantly alter the dopamine signals of the lesioned group. Taken together, in addition to the increased lipid peroxidation in SN, our in vivo electrochemical data demonstrates that iron-induced oxidative injury attenuates K+-evoked dopamine release and dopamine uptake in the ipsilateral striatum. The diminished nomifensine effect implies a lack of high-affinity dopamine uptake sites.

Animals↗

PubMed1998

Neuroprotection by S-nitrosoglutathione of brain dopamine neurons from oxidative stress.

The proposed anti- and pro-oxidant effects of nitric oxide (NO) derivatives, such as S-nitrosoglutathione (GSNO) and peroxynitrite, were investigated in the rat nigrostriatal dopaminergic system. Intranigral infusion of freshly prepared GSNO (0-16.8 nmol, i.n.) prevented iron-induced (4.2 nmol, i.n.) oxidative stress and nigral injury, reflected by a decrease in striatal dopamine levels. This neuroprotective effect of GSNO was verified by ex vivo imaging of brain dopamine uptake sites using 125I-labeled RTI-55. In addition, in vitro data indicate that GSNO concentration-dependently inhibited iron-evoked hydroxyl radical generation and brain lipid peroxidation. In this iron-induced oxidant stress model, GSNO was approximately 100-fold more potent than the antioxidant glutathione (GSH). Light-exposed, NO-exhausted GSNO produced neither antioxidative nor neuroprotective effects, which indicates that NO may mediate at least part of GSNO's effects. Moreover, GSNO completely (and GSH only partially) inhibited the weak pro-oxidant effect of peroxynitrite, which produced little injury to nigral neurons in vivo. This study provides relevant in vivo evidence suggesting that nanomol GSNO can protect brain dopamine neurons from iron-induced oxidative stress and degeneration. In conclusion, S-nitrosylation of GSH by NO and oxygen may be part of the antioxidative cellular defense system.

Animals↗

PubMed1997

Paramedian reticular nucleus may be unrelated to the development of hypertension in spontaneously hypertensive rats.

The role of paramedian reticular nucleus (PRN), a structure effecting sympathetic inhibition, in the development of hypertension was investigated in young spontaneously hypertensive rats (SHR) and two age-matched normotensive rats, Wistar-Kyoto (WKY) and Sprague-Dawley rats (SD). Three different experimental manipulations, including electrical-lesioning, sham-operated and intact control, were performed in SHR, WKY and SD rats 7 weeks after birth. In the control groups, the systolic arterial blood pressure (SABP) of SHR increased abruptly from 160 mmHg to 230 mmHg from the 6th to 13th week after birth, whereas those of WKY and SD maintained a normal range of SABP. In the lesioned groups, a hypotension and/or bradycardia was evoked by electrical stimulation to verify the location of PRN. Following the verification, a direct current was delivered to lesion the PRN in situ. The effect of PRN lesioning on the subsequent development of hypertension was illustrated by comparing SABP in three experimental groups of age-matched conscious SHR, WKY and SD during 8-13 weeks after birth. We found that the average SABP in the lesioned SHR was consistently elevated and was not significantly different from those of the sham-operated and the control. In contrast, in the normotensive rats, there was no significant increase in SABP within the three experimental groups, i.e., the average SABP of the lesioned, the shamed-operated and the control group maintained a normal range. Our results support the contention that the hypertension of SHR developed within 6-13 weeks after birth. In addition, the sympatho-inhibitory mechanism of PRN was not directly related to the development of hypertension.

Aging↗

PubMed1997

Effects of ethanol and nomifensine on NE clearance in the cerebellum of young and aged Fischer 344 rats.

Rapid chronoamperometric recordings coupled with local application of drugs by pressure ejection were used to investigate the effects of nomifensine and ethanol (EtOH) on exogenous norepinephrine (NE) clearance in the cerebellum of young (5-month-old) and aged (24-26-month-old) male Fischer 344 rats. In the young rats, local nomifensine application prolonged exogenous NE clearance, indicating transporter mediated uptake inhibition. NE clearance was modestly but significantly prolonged in the aged rats as compared to the young rats, suggesting less efficient uptake. Consistent with this, there was little effect of nomifensine on NE clearance in the aged rats. In contrast to the effect of nomifensine, EtOH inhibited NE clearance in both young and aged rats. These data further support the hypothesis that one effect of EtOH in cerebellar NE systems is inhibition of NE uptake into NE-containing nerve terminals, and they also demonstrate that the effect of nomifensine on exogenous NE clearance in vivo in the cerebellum is altered by the aging process, while the effect of EtOH is not.

Aging↗

PubMed1996

S-nitrosothiols and nitric oxide, but not sodium nitroprusside, protect nigrostriatal dopamine neurons against iron-induced oxidative stress in vivo.

Intranigral infusion of ferrous citrate (4.2 nmol) induced an acute lipid peroxidation in the substantia nigra and a chronic dopamine depletion in the striatum of rat nigrostriatal system. Coinfusion of 8.4 nmol nitric oxide donors such as S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP) or nitric oxide (approximately 2 nmol) protected nigrostriatal neurons against iron-induced lipid peroxidation and associated oxidative injury. However, sodium nitroprusside (SNP, 8.4 nmol) augmented dopamine depletion caused by ferrous citrate because SNP is a ferricyanide complex. The present in vivo results indicate that nitric oxide and S-nitrosothiols are antioxidants which can protect brain dopamine neurons against oxidant stress/damage.

Animals↗

PubMed1996

Angiotensin II activates pressor and depressor sites of the pontomedulla that react to glutamate.

1. In cats anaesthetized with a mixture of alpha-chloralose (40 mg/kg) and urethane (400 mg/kg) and in rats anaesthetized with a mixture of alpha-chloralose (60 mg/kg) and urethane (800 mg/kg), changes in systemic arterial pressure (SAP), heart rate (HR) and sympathetic activities of vertebral (VNA) and renal (RNA) nerves were determined following the microinjection of angiotensin II (AngII; 0.16 mmol/L; 50 nL) into the pressor and depressor sites of the pontomedulla previously reacted to a microinjection of monosodium L-glutamate (Glu; 0.1 mol/L; 50 nL). Pressor sites included gigantocellular tegmental field (FTG) and dorsal medulla (DM) and rostral ventrolateral medulla (VLM). The depressor site was the caudal VLM (CVLM). The effects of losartan (1 mmol/L; 50 nL), a specific AT1 receptor non-peptide antagonist for AngII, on responses induced by AngII in the VLM, DM and CVLM were also determined. 2. In 30% of pressor sites in the FTG, 55% in the VLM and 67% in the DM and in 76% of depressor sites in the CVLM previously exposed to Glu, microinjection of AngII to the same site produced pressor or depressor responses similar to that of Glu, but smaller in magnitude, particularly in the pressor VLM. Changes in both VNA and RNA induced by AngII were also smaller than those induced by Glu, particularly RNA from DM activation. 3. In the dorsal motor nucleus of the vagus, AngII, as Glu, produced marked bradycardia, but again this was smaller in magnitude than the bradycardia produced by Glu. 4. In rats, in the DM near or around the nucleus of the solitary tract where Glu increased SAP, microinjection of AngII (0.8 mmol/L; 60 nL) produced a depressor response, while the microinjection of 1.6 mmol/L (60 nL) AngII produced a pressor response. 5. Losartan blocked the increase in SAP induced by AngII in the VLM and DM. Decreases in SAP induced by AngII in the CVLM, however, were only slightly decreased by losartan. 6. Our data suggest that a significant portion of pressor and depressor sites of the pontomedulla contain neurons responsive to both AngII and Glu. In neurons in the VLM and DM, AngII produced pressor responses that were primarily mediated through AT1 receptors, while the depressor actions of AngII in the CVLM were not mediated by AT1 receptors.

Angiotensin II↗

PubMed1995

Dynamic analysis of ethanol effects on NMDA-evoked dopamine overflow in rat striatum.

This study was undertaken to dynamically examine the effects of ethanol on the striatal dopaminergic transmission, in terms of N-methyl-D-aspartate (NMDA)-evoked dopamine release and dopamine uptake. In the striatum of urethane-anesthetized Sprague-Dawley rats, extracellular dopamine was measured using in vivo electrochemical detection coupled with a nafion-coated carbon fiber working electrode. Micro-ejection of NMDA evoked a transient dopamine release from the dopamine-containing nerve terminals in striatum. Local application of ethanol by pressure ejection did not elicit significant changes in spontaneous dopamine release. However, with ethanol pretreatment, the time course of NMDA-induced dopamine release was markedly prolonged while the magnitude and the rate of clearance were significantly reduced. These effects were compared to those of nomifensine, a dopamine uptake blocker. Nominfensine pretreatment was found to augment the time course of NMDA-evoked dopamine release analogous to those by ethanol pretreatment. Furthermore, pretreatment with ethanol did not increase the time course parameters of dopamine signals if dopamine releases were induced by co-application of NMDA and nominfensine. These data suggest that in addition to the attenuation of NMDA-evoked dopamine release, ethanol inhibits dopamine uptake in a similar fashion to that observed with nomifensine in situ in the striatum. Indeed, ethanol altered the uptake of exogenous dopamine from the extracellular space of striatal cortex. The time course of dopamine signals was prolonged and the rate of clearance was reduced after ethanol treatment. Taken together, our data demonstrate that ethanol simultaneously inhibits NMDA-evoked dopamine release and dopamine uptake in the striatum, suggesting the importance of the interplay between release and uptake in ethanol effects on striatal dopaminergic transmission.

Animals↗

PubMed1995

Involvement of nitric oxide in dopaminergic transmission in rat striatum: an in vivo electrochemical study.

In vivo electrochemical detection with a Nafion-coated carbon fiber working electrode, which provides information on the spatial and temporal dynamics of dopamine overflow, was used to investigate the involvement of nitric oxide (NO) in the dopaminergic transmission in the striatum of urethane-anesthetized Sprague-Dawley rats. A mixture of N-methyl-D-aspartate (NMDA) and nomifensine, a dopamine uptake blocker, was locally pressure-ejected to elicit a transient dopamine overflow from the dopamine-containing nerve terminals in the striatum. Local application of N omega-nitro-L-arginine methyl ester (L-NAME), which blocks endogenous NO formation, increased the magnitude of dopamine/release evoked by a subsequent NMDA and nomifensine application but resulted in no significant alteration in the time course. Furthermore, microejection of L-arginine, an NO precursor, or sodium nitroprusside (SNP), an NO generator, did not cause detectable changes in dopamine level in the striatal extracellular space. However, NMDA-induced dopamine release was profoundly inhibited with L-arginine or SNP pretreatment. In addition, NO affects dopamine uptake in rat striatum. Exogenous dopamine applied through a micropipette, reversibly and reproducibly, elicited an electrochemical signal. The time course of these signals was significantly prolonged by L-NAME treatment. These data suggest that NO is diversely involved in regulating dopaminergic transmission in rat striatum.

Animals↗

PubMed1994

Pineal nitric oxide synthase: characteristics, adrenergic regulation and function.

Available studies indicate that the adrenergic stimulation of pineal cyclic GMP production involves stimulation of guanylyl cyclase activity by nitric oxide (NO) derived from arginine. This line of investigation was extended in the present study. Using a highly sensitive microassay, it was found that pineal NO synthase activity is present at levels approximately 30% of those in the cerebellum, that approximately 95% of enzyme activity is cytoplasmic, that the enzyme is Ca2+/calmodulin-dependent and that enzyme activity is inhibited by the arginine analog NG-nitro-L-arginine methyl ester (L-NAME). Norepinephrine treatment of intact glands in culture increased [3H]citrulline formation from [3H]arginine. This treatment also increased the formation of an NO-like compound, indicating that NO synthase activity in the intact gland is elevated by adrenergic stimulation. Studies on the effects of inhibition of NO synthase activity indicated that treatments known to inhibit NO synthase activity and the adrenergic stimulation of cyclic GMP accumulation did not inhibit adrenergic stimulation of pineal cyclic AMP, N-acetyltransferase activity or melatonin production. These observations support the hypothesis that NE stimulation of pineal cyclic GMP accumulation involves stimulation of a Ca2+/calmodulin-sensitive form of NO synthase, resulting in enhanced accumulation of NO; and, that although NO appears to play a role in the adrenergic stimulation of pineal cyclic GMP accumulation, it does not appear to play a critical role in the adrenergic stimulation of cyclic AMP, N-acetyltransferase activity or melatonin production.

Amino Acid Oxidoreductases↗