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G J Liu

Publications and source records attributed to G J Liu.

At least 19 recordsLinked to original sources
PubMed1998

Modulatory action of PACAP27 on NMDA receptor channel activity in cultured chick cortical neurons.

The modulatory effect of PACAP27 on NMDA receptor channel activity in cultured chick cortical neurons was investigated using the outside-out recording mode of the patch clamp technique. Channel opening frequency elicited by 20 microM NMDA, or 20 microM NMDA plus 1 microM glycine, was potentiated in the presence of 100 nM PACAP27 and inhibited with 1000 nM PACAP27. These effects were reversible on washout and reduced when glycine concentration was increased to 10 microM, but were not affected by the PACAP antagonist PACAP6-27 (1 microM) or the GTP inhibitor GDP-beta-S (100 microM). It is suggested that PACAP27 may exert its modulatory action on NMDA receptor channel activity through the glycine site(s).

Animals↗
PubMed1997

PACAP38 modulates activity of NMDA receptors in cultured chick cortical neurons.

The outside-out recording mode of the patch-clamp technique was used to study modulatory effects of pituitary adenylate cyclase-activating polypeptide (PACAP38) on N-methyl--aspartate (NMDA) receptor activity in cultured chick cortical neurons. Biphasic concentration-dependent effects of PACAP38 on channel opening frequency induced by NMDA (20 microM) and glycine (1 microM) were found, with low concentrations (0.5-2 nM) of PACAP38 increasing activity and higher concentrations (10-1,000 nM) causing inhibition. These effects were reversible, reduced with higher concentrations of glycine (2-10 microM) but not by 200 microM NMDA, and inhibited by 10 microM 7-chlorokynurenic acid. In addition, 1 microM PACAP6-38 (a PACAP antagonist) inhibited channel activity due to 20 microM NMDA and 1 microM glycine by 66%, and this inhibition was reduced to 13% in the additional presence of 2 nM PACAP38. These observations suggest that PACAP38 has a direct modulatory effect on the NMDA receptor that is independent of intracellular second messengers and probably mediated through the glycine coagonist site(s).

Animals↗
PubMed1996

Multiple intracellular signal transduction pathways mediating inward current produced by the neuropeptide, achatin-I.

The effects of intracellular signal transduction system inhibitors on the inward current (Iin) caused by achatin-I (Gly-D-Phe-Ala-Asp), an Achatina endogenous tetrapeptide having a D-phenylalanine residue, applied locally onto the neurone tested, were examined under voltage clamp using two identifiable Achatina giant neurone types, v-RCDN (ventral-right cerebral distinct neurone) and PON (periodically oscillating neurone). H-89 (N-[2-(p-bromocinnamylamino)-ethyl]-5-isoquinolinesulfonamide) (adenosine-3',5'-cyclic monophosphate (cyclic AMP)-dependent protein kinase inhibitor) markedly suppressed the achatin-I-induced Iin on PON, whereas this drug was ineffective on the Iin of v-RCDN. Dose (pressure duration)-response study of achatin-I on PON in a physiological solution and in the presence of H-89, and Lineweaver-Burk plot of these data, indicated that H-89 inhibited the Iin in a noncompetitive manner. KT5823 (N-methyl-(8R*,9S*,11S*)-(-)-9-methoxy-9-methoxycarbonyl-8-methyl-2,3,9, 10-tetrahydro-8,11-epoxy-1H,8H,11H-2, 7b,11a-triazadibenzo[a,g]cycloocta[c,d,e]-trinden-1-on e) (guanosine-3',5'-cyclic monophosphate (cyclic GMP)-dependent protein kinase inhibitor) suppressed the achatin-I-induced Iin of v-RCDN in mainly noncompetitive and partly uncompetitive manners, but this drug had no effect on the Iin of PON. W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide) (calmodulin inhibitor) suppressed noncompetitively the Iin of PON, but this drug had no effect on the Iin of v-RCDN. IBMX (3-isobutyl-1-methylxanthine) (cyclic nucleotide phosphodiesterase inhibitor) enhanced the achatin-I-induced Iin of v-RCDN, but this drug was ineffective on the Iin of PON. However, IBMX might have effects on the achatin-I receptor sites on v-RCDN. These findings suggest multiple intracellular signal transduction pathways mediating the achatin-I-induced Iin: the Iin of PON is via cyclic AMP-dependent and probably Ca2+/calmodulin-dependent protein kinases, and that of v-RCDN via cyclic GMP-dependent protein kinase. Other signal transduction system inhibitors including calphostin C (2-[12-[2-(benzyloxy)-propyl]-3, 10-dihydro-4,9-dihydroxy-2,6,7,11-tetramethoxy-3,10-dioxo-1-per yleny]-1 -methylethyl carbonic acid 4-hydroxyphenyl ester) (protein kinase C inhibitor) did not significantly affect the Iin of both v-RCDN and PON.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Anoxic injury of endothelial cells increases production of nitric oxide and hydroxyl radicals.

Reactive oxygen radicals have been implicated as mediators of anoxic injury in brain, but the cellular source of these radicals is unknown. In the periphery, there is evidence that endothelial cells play a fundamental role in anoxic tissue injury. The objective of the present study was to examine the response of rat brain endothelial cells to anoxia/reoxygenation injury in vitro. The results demonstrate that brain endothelial cells produce hydroxyl radicals and have increased nitric oxide synthase activity after anoxic injury. The increased production of nitric oxide in the cerebral endothelial cells does not appear to be mediated by an increase in either inducible or constitutive nitric oxide synthase. The radical trap alpha-phenyl-tert-butyl nitrone blocked hydroxyl free radical production, but not nitric oxide. These data suggest that the cerebral microcirculation may be an important site of oxygen free radical production in the brain in ischemic stroke.

Aerobiosis↗
PubMed1996

Effects of L-glutamic acid and its agonists on snail neurones.

The sensitivities of 22 giant neurone types of an African giant snail (Achatina fulica Férussac) to threo-beta-hydroxy-L-glutamic acid (threo-L-BHGA), a derivative of L-glutamic acid (L-Glu), applied by brief pneumatic pressure ejection, were examined under current clamp. The 5 neurone types were depolarized by this compound, whereas 2 were hyperpolarized. The 4 neurone types, PON (periodically oscillating neurone), RAPN (right anterior pallial nerve neurone), d-RPLN (dorsal-right parietal large neurone) and RPeNLN (right pedal nerve large neurone) that are excited by threo-L-BHGA and one type, v-LCDN (ventral-left cerebral distinct neurone), inhibited by this compound, were selected to study their pharmacological features in detail. Effects of the stereoisomers of L-Glu and threo-L-BHGA, and mammalian L-Glu receptor agonists, ejected by brief pressure, on the 5 Achatina neurone types were examined under voltage clamp. d-RPLN produced an inward current (Iin) by L-Glu and threo-L-BHGA, whereas this neurone type was insensitive to D-Glu and erythro-L-, threo-D- and erythro-D-BHGA. This was also excited by AMPA, indicating that the pharmacological features of the L-Glu receptors in this neurone type were similar to those of the mammalian ionotropic AMPA type L-Glu receptors. RAPN produced Iin by L-Glu and threo-L-BHGA. This neurone type was also excited by quisqualic acid and ibotenic acid, indicating that the features of the L-Glu receptors were similar to those of the mammalian metabotropic L-Glu receptors. PON and RPeNLN produced Iin by L-Glu and threo-L-BHGA. These neurone types were also excited by quisqualic acid, AMPA and ibotenic acid, indicating that their L-Glu receptors seemed to be in the mixed type, of the two types mentioned. On the other hand, v-LCDN produced an outward current (Iout) by threo-L- and erythro-L-BHGA, but was insensitive to L-Glu, indicating that the receptors activated by L-BHGA were not L-Glu receptors. This neurone type was also inhibited by quisqualic acid.

Animals↗
PubMed1996

Association between reactive oxygen species and disease activity in chronic hepatitis C.

Reactive Oxygen Species (ROS) may be involved in the damage occurring in the course of chronic HCV infection. Individuals with chronic hepatitis C present increased hepatic levels of malondialdehyde (MDA) and reduced levels of glutathione. To determine whether these observations are associated with serological evidence for ROS injury, MDA and protein carbonyl content (PCC) of serum was determined in 20 HCV positive patients (14 chronic active hepatitis -- CAH and 6 cirrhosis) and 20 controls. Compared to controls, HCV positive subjects had increased levels of MDA (13.33 +/- 0.21 SE ng/ml vs. 9.90 +/- 0.65 P < .05) and PCC (4.74 +/- 0.21 mmol/mg vs 3.68 +/- 0.21, p < .02). Patients with CAH had higher levels than did cirrhotics. Both MDA and PCC correlated with serum ALT levels (r = .792 and r = .818 respectively, p < .001). A common origin for MDA and PCC found in patients with chronic hepatitis C was suggested by the correlation between the two measures (r = .741, p < .001). No correlation were found between MDA or PCC and the hepatic iron content. These data demonstrate that: (1) lipid and protein oxidation occur in chronic hepatitis C, (2) oxidative damage can be demonstrated as increased serum levels of MDA and PCC, and (3) both MDA and PCC levels correlate with disease activity.

Adult↗
PubMed1996

Biphasic effect of pentobarbitone on chick myotube nicotinic receptor channel kinetics.

1. The modulatory action of pentobarbitone on chick myotube nicotinic acetylcholine receptor kinetics was studied by the patch clamp technique, particularly focussing on effects at low concentrations. 2. Open time sojourn distributions of foetal-type receptors recorded at room temperature (22-24 degrees C) in cell-attached mode in the presence of 0.2 microM acetylcholine were well described by two exponentials, with fast and slow time constants of 0.53 +/- 0.12 and 16.7 +/- 2.2 ms (means +/- s.e. mean) respectively. 3. The duration of the slow open time constant was increased by low concentrations of pentobarbitone (up to 1 microM), and thereafter decreased with higher concentrations (10-50 microM) in a concentration-dependent manner. 4. Complementary evidence for the stimulatory effect of pentobarbitone on open time was obtained (i) by using a backfill technique where drug concentration at the patch gradually increases over time, and (ii) through use of perfused outside-out preparations where receptors in the same patch were successively exposed to acetylcholine in the absence and presence of pentobarbitone. 5. The dual action of pentobarbitone on channel kinetics probably, indicates that an allosteric interaction mechanism is involved rather than simple steric channel blockade.

Animals↗
PubMed1996

Enhancing effect of essential oils on the penetration of 5-fluorouracil through rat skin.

Three essential oils as penetration enhancers for 5-fluorouracil (5-FU) were studied using excised rat skin. The oils used were eucalyptus, peppermint and turpentine. Azone was used for comparison. The enhancing effect of the oils was found to be less than that of azone, but all the oils used enhanced the permeation of 5-FU. Eucalyptus oil was found to be the most active, causing about 60 fold increase, while peppermint and turpentine caused 46 and 28 fold increase, respectively. Eucalyptus oil was further studied by grading it into 5 fractions according to difference in boiling points. It was found that their activities increased as their boiling point increased. With all enhancers increased partition coefficients were observed but the diffusion coefficient values obtained were comparatively higher. The mode of action of these accelerants may be described by combined processes of partition and diffusion, the diffusion process being dominant.

Administration, Cutaneous↗
PubMed1995

Effects of dopamine on snail neurones.

The pharmacological features of dopamine receptors in identifiable giant neurone types of a snail (Achatina fulica Férussac) were studied. Under voltage clamp, two neurone types, LVMN (left ventral multiple spike neurone) and d-RPeAN (dorsal-right pedal anterior neurone), produced an inward current (Iin) in response to dopamine, (-)-noradrenaline and epinine, whereas v-LCDN (ventral-left cerebral distinct neurone) produced an outward current (Iout) in response to dopamine and epinine. Mammalian dopamine receptor agonists, fenoldopam (dopamine D1-like receptor agonist), (+/-)-SKF 38393 (1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8- diol) (D1-like), apomorphine (D2-like), (-)-quinpirole (D3 and D4) and methylergometrine showed slight or no effect. (+/-)-SKF 83566 ((+/-)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benza zepine) (dopamine D1-like receptor antagonist) and (+)-UH 232 (cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin) (D3 and D2) non-competitively inhibited the Iin of LVMN and d-RPeAN, but (+/-)-sulpiride (D2-like) was without effect. In contrast, (+/-)-sulpiride competitively inhibited Iout of v-LCDN, (+)-UH 232 non-competitively inhibited Iout of v-LCDN but (+/-)-SKF 83566 was without effect. H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine) (non-selective protein kinase inhibitor) inhibited Iin of LVMN and d-RPeAN, but did not affect Iout of v-LCDN. Dopamine-induced Iin was Na(+)-dependent; Iout was K(+)-dependent. Ouabain did not affect these currents. We propose that the pharmacological features of Achatina neuronal dopamine receptors are not fully comparable to those of mammals, although intracellular signal transduction systems linked with dopamine receptors may similarly exist in different animal species.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1995

Blockers for excitatory effects of achatin-I, a tetrapeptide having a D-phenylalanine residue, on a snail neurone.

Some histamine H1 receptor antagonists suppressed the inward current (Iin) of an Achatina identifiable neurone type, PON (periodically oscillating neurone), caused by an Achatina endogenous tetrapeptide having a D-phenylalanine residue, achatin-I (Gly-D-Phe-Ala-Asp), under voltage clamp. Achatin-I was applied locally to the neurone by brief pneumatic pressure ejection and antagonists were administered by perfusion. The dose-response curves of the effective histamine H1 antagonists indicated their potency order to suppress the Iin as follows: chlorcyclizine, promethazine, triprolidine and homochlorcyclizine > trimeprazine and clemastine > diphenylpyraline. The potent drugs were mostly piperazine and phenothiazine types. The effects of chlorcyclizine, promethazine and triprolidine on the dose (the duration of the pressure ejection)-response curve of achatin-I indicated that these drugs affected the Iin caused by achatin-I in a non-competitive manner. The antagonists for the receptors of the small-molecule neurotransmitters other than histamine H1, such as histamine H2, acetylcholine, gamma-aminobutyric acid (GABA), L-glutamic acid, dopamine, alpha- and beta-adrenalin and 5-hydroxytryptamine, had no effect on the Iin caused by achatin-I.

Amino Acid Sequence↗
PubMed1995

Suppressing effects of neuroactive peptides on the inward current caused by achatin-I, an Achatina endogenous peptide.

1. Modulatory effects of the four molluscan neuroactive peptides. FMRFamide (Phe-Met-Arg-Phe-NH2), APGW-amide (Ala-Pro-Gly-Trp-NH2), oxytocin and [SER2]-Mytilus inhibitory peptide ([SER2]-MIP) (Gly-Ser-Pro-Met-Phe-Val-NH2) were examined on the inward current (Iin) caused by achatin-I (Gly-D-Phe-Ala-Asp), which has been isolated from the Achatina ganglia. 2. Two Achatina giant neurone types, v-RCDN (ventral-right cerebral distinct neurone) and PON (periodically oscillating neurone), were used. Achatin-I was applied locally to the neurone tested by brief pneumatic pressure ejection, and the other molluscan neuroactive peptides were perfused around the ganglia. 3. FMRFamide, perfused at 3 microM, suppressed markedly the Iin elicited by the achatin-I of both v-RCDN and PON. APGW-amide at 3 microM also suppressed the Iin of v-RCDN, but did not affect that of PON. Oxytocin at 1 microM suppressed the Iin of PON, but did not affect that of v-RCDN. [Ser2]-MIP at 3 microM did not affect the Iin of v-RCDN. 4. The dose-response curves of FMRFamide, APGW-amide and oxytocin, indicated that their respective suppressive effects on the Iin of achatin-I were dose-dependent, and that APGW-amide was slightly more potent than the other peptides. The dose (pressure duration)-response curves of achatin-I (1 kg/cm2, 10(-3) M, 5 min interval), obtained by varying the duration of the achatin-I pressure ejection, were measured in the presence and absence of each of the three peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Further mapping of the Achatina giant neurone types sensitive to the neuroactive peptides isolated from invertebrates.

1. The effects of the 10 synthetic neuroactive peptides originally isolated from invertebrates, applied locally to the neurone tested by the brief pneumatic pressure ejection on the identifiable neurone types of Achatina fulica Ferussac were examined. 2. Achatin-1 (Gly-D-Phe-Ala-Asp), an Achatina endogenous tetrapeptide having a D-phenylalanine residue, ejected locally, showed the depolarizing effects on nearly half of the number of neurone types tested. 3. ACEP-1 (Ser-Gly-Gln-Ser-Trp-Arg-Pro-Gln-Gly-Arg-Phe-NH2), isolated originally from Achatina atria, and pedal peptide (Pro-Leu-Asp-Ser-Val-Tyr-Gly-Thr-His-Gly-Met-Ser-Gly-Phe-Ala) and buccalin (Gly-Met-Asp-Ser-Leu-Ala-Phe-Ser-Gly-Gly-Leu-NH2), found in Aplysia neurones, showed excitatory effects on some Achatina neurone types. 4. Myomodulin (Pro-Met-Ser-Met-Leu-Arg-Leu-NH2), found in Aplysia neurones, produced a hyperpolarization on nearly half of the number of Achatina neurone types tested. The two FMRFamide-like peptides, <EDPFLRFamide (<Glu-Asp-Pro-Phe-Leu-Arg-Phe-NH2), isolated from Helix heart, and AF1 (Lys-Asn-Glu-Phe-Ile-Arg-Phe-NH2), from Ascaris head, also showed hyperpolarizing effects on more than half of the number of Achatina neurone types. 5. SALMFamide 1 (Gly-Phe-Asn-Ser-Ala-Leu-Met-Phe-NH2), isolated from Asterias nervous system, CCAP (Pro-Phe-Cys-Asn-Ala-Phe-Thr-Gly-Cys-NH2), from Carcinus pericardial organ, and corazonin (<Glu-Thr-Phe-Gln-Tyr-Ser-Arg-Gly-Trp-Thr-Asn-NH2), from Periplaneta cardiac corpus, had no effect on Achatina neurones.

Amino Acid Sequence↗
PubMed1994

Mechanism of intraocular pressure decrease after contact transscleral continuous-wave Nd:YAG laser cyclophotocoagulation.

Twenty-two eyes of 11 cynomolgus monkeys were subjected to contact transscleral cyclophotocoagulation with a continuous-wave Nd:YAG laser. The right eye of each monkey was coagulated at the pars plicata region by the contact probe placed 1.0 mm from the limbus, while the left eye of each monkey was coagulated at the pars plana region by the contact probe placed 3.0 mm from the limbus. Physiological and morphological studies were carried out up to 6 months after the treatment. The postoperative intraocular pressure showed a significant decrease within 1 week, corresponding to the inflammation of the anterior chamber. A gradual increase of the intraocular pressure occurred from the 2nd week on and returned to the preoperative value 8 weeks after pars plicata coagulation. The pars plana coagulation group maintained the intraocular pressure lower than the preoperative value until the end of the observation period. Histopathological examinations were carried out by the use of tracer particle perfusion into the anterior chamber. The pathologic features of pars plicata coagulation were necrosis, followed by atrophy of the ciliary process. The tracer particles accumulated at the anterior portion of the space between the bundles of ciliary muscle. The pathologic features of pars plana coagulation were necrosis followed by extension of proliferative tissue into the vitreous. The surrounding extracellular space of the stroma was enlarged, and the ciliary muscles were separated from the sclera. The tracer particles accumulated at the enlarged extracellular space of the stroma and the opened suprachoroidal space. These results suggest that the decrease of the intraocular pressure after pars plicata cyclocoagulation resulted from the reduction of aqueous secretion, whereas that after pars plana cyclocoagulation resulted from enhancement of the uveoscleral outflow through the enlarged extracellular space from the anterior chamber into the suprachoroidal space.

Animals↗
PubMed1993

Modulation of neuropeptide effects by achatin-I, an Achatina endogenous tetrapeptide.

Achatin-I (Gly-D-Phe-L-Ala-L-Asp), an endogenous tetrapeptide in the ganglia of Achatina fulica Férussac, at 3 x 10(-6) M suppressed both the inward current (Iin) of an Achatina giant neurone, PON (periodically oscillating neurone), caused by locally ejected oxytocin, and the outward current (Iout) of v-RCDN (ventral-right cerebral distinct neurone) induced by APGW-amide. Dose (pressure duration)-response studies with oxytocin and APGW-amide showed that their ED50 values were not affected by achatin-I, whereas the Emax values were suppressed. The v-RCDN Iout caused by FMRF-amide was enhanced by achatin-I, but the same current induced by [Ser2]Mytilus inhibitory peptide ([Ser2]MIP) was not affected. Achatin-I suppressed the Iout of TAN (tonically autoactive neurone) caused by acetylcholine, but did not affect the Iin of v-RCDN elicited by acetylcholine. The Iout caused by gamma-aminobutyric acid, threo-beta-hydroxy-L-glutamic acid and dopamine was not affected by achatin-I. It is considered that achatin-I acts as a neuromodulator and has both suppressing and enhancing actions on the effects of various neurotransmitters, including peptides, in Achatina giant neurones.

Acetylcholine↗
PubMed1993

Modulatory effects of achatin-I, an Achatina endogenous neuroactive peptide, on responses to 5-hydroxytryptamine.

Achatin-I (Gly-D-Phe-L-Ala-L-Asp) was found in the ganglia of an African giant snail (Achatina fulica Férussac), and proposed as an excitatory neurotransmitter of Achatina neurones. At 3 x 10(-6) the peptide markedly enhanced the fast inward current (Iin) of an Achatina neurone type, TAN (tonically autoactive neurone), produced by the pneumatic pressure ejection of 5-HT. This Iin was facilitated immediately by the achatin-I perfusion, and the facilitation decreased gradually even with the peptide present. The dose (duration)-response curves of the TAN fast Iin on pressure ejection in the absence (control) and presence of achatin-I at 3 x 10(-6) M (n = 8) were analyzed as follows. The ED50 (95% confidence limit) were 59.3 ms (13.9-95.3 ms) for the control, and 36.5 ms (19.5-52.6 ms) for achatin-I. The Emax were 1.06 +/- 0.11 nA for the control, and 1.74 +/- 0.26 nA for achatin-I (P < 0.01 for paired data). Among achatin-I derivatives, achatin-II (Gly-L-Phe-L-Ala-L-Asp) enhanced the TAN fast response to 5-HT, but was ten times weaker than achatin-I. [L-Glu4]achatin-I (Gly-D-Phe-L-Ala-L-Glu) and achatin-I amide (Gly-D-Phe-Ala-L-Asp-NH2) had no facilitatory effect. We propose that achatin-I is a neuromodulator as well as a neurotransmitter for Achatina giant neurones.

Amino Acid Sequence↗
PubMed1993

AJ-2615, a long-acting Ca2+ channel antagonist with a novel structure.

AJ-2615, a dihydrodibenzothiepin derivative, at 10(-4) M inhibited the peak ICa amplitude of an identifiable Achatina neurone, PON (periodically oscillating neurone), by nearly a half of the control response 30 min after the start of perfusion (ED50: 0.96 x 10(-4) M). The ICa inhibition was still sustained 30 min after washout, indicating that AJ-2615 has long-lasting activity. The compound inhibited the ICa over a wide range of membrane potentials depolarized by the voltage pulse (Vd), but did not change the membrane potential required to produce the maximal ICa (Vd = 0 mV). The additional decrease in ICa amplitude caused by changing from low-frequency (1/5 min) depolarizing pulses to high-frequency (3/min) depolarizing pulses in the presence of AJ-2615 at 10(-4) M was 39.2 +/- 4.5% (mean+S.E.M.; n = 5), indicating use dependence. The steady state inactivation curves were measured in the presence or absence of AJ-2615 at 10(-4) M with a depolarizing prepulse (Vd = varied, duration = 30 s) followed by a depolarizing test pulse (Vd = +10 mV, duration 80 ms), with 2 ms intervals (n = 3): the ratio of AJ-2615 dissociation constant in the resting Ca2+ channel (Kr) and in the inactivated Ca2+ channel (Ki), Kr/Ki, was calculated to be 9.6:1, indicating voltage dependence.

Animals↗
PubMed1993

Anoxia/reoxygenation induces hydroxyl free radical formation in brain microvessels.

Isolated rat brain microvessels have been utilized to examine whether they produce hydroxyl free radicals if they are subjected to a 10- to 20-min anoxia period followed by a 40-min reoxygenation period. Hydroxyl free radical flux was assessed utilizing salicylate as a trap. The 2,3- and 2,5-dihydroxybenzoic acids (DHBA) products as well as salicylate in the microvessels were quantitated utilizing high-pressure liquid chromatography (HPLC) with electrochemical and fluorescence detection. The results show that a period of anoxia followed by reoxygenation resulted in an enhanced formation of DHBA compared to the normoxic control microvessels. Addition of superoxide dismutase (SOD) and catalase to the microvessels undergoing anoxia decreased the amount of hydroxyl free radicals trapped, suggesting that superoxide and hydrogen peroxide were produced and excreted from the endothelial cell surfaces and then unless quenched reentered the cells to form hydroxyl free radicals within. The amount of 2,5-DHBA formed closely correlated with the amount of 2,3-DHBA formed, indicating that either product can be used to assess hydroxyl free radical flux in brain microvessels.

Animals↗