Biomedical subjects

J Y Chan

Publications and source records attributed to J Y Chan.

At least 73 records · Page 4Linked to original sources

PubMed1997

Enhancement of spontaneous baroreflex by antisense c-fos oligonucleotide treatment in the NTS of the rat.

We evaluated the hypothesis that basal Fos protein at the nucleus tractus solitarii (NTS), the primary terminal site for baroreceptor afferents, exerts a tonic inhibitory modulation on the spontaneous baroreceptor reflex (BRR) control machinery, which is responsible for beat-to-beat regulation of resting systemic arterial pressure (SAP). In adult male Sprague-Dawley rats anesthetized and maintained with pentobarbital sodium, microinjection bilaterally into the caudal NTS of a 15-mer antisense oligonucleotide that targets against the initiation codon of c-fos mRNA (5'-129 to 143-3') significantly enhanced the spontaneous BRR response, as determined by transfer function analysis of SAP and heart rate signals. The same treatment also diminished baseline Fos-like immunoreactivity in the absence of acute cardiovascular perturbation. Control treatments with artificial cerebrospinal fluid, sense cDNA, or antisense oligonucleotides that either target against a different site of the c-fos mRNA (5'-135 to 149-3') or with three mismatched nucleotides in the antisense sequence, were ineffective. These observations support the notion that, under minimal cardiovascular perturbation, basal expression of Fos protein in the NTS may represent an early step in the cascade of intracellular events that leads to long-term inhibitory modulation of beat-to-beat baroreflex control of blood pressure.

Afferent Pathways↗

PubMed1996

Participation of Fos protein at the nucleus tractus solitarius in inhibitory modulation of baroreceptor reflex response in the rat.

We investigated the physiologic role of Fos protein at the nucleus tractus solitarius (NTS) in the modulation of baroreceptor reflex (BRR) in adult, male Sprague-Dawley rats that were anesthetized and maintained with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v. infusion supplements). Repeated and scheduled activation of the baroreceptors by transient hypertension induced by i.v. administration of phenylephrine (2.5, 5.0 or 10.0 micrograms/kg) resulted in a significant increase in Fos-like immunoreactivity (Fos-LI), primarily in the caudal part of the NTS. This increase in Fos-LI in the barosensitive NTS neurons was appreciably reduced by bilateral microinjection into the caudal NTS of an antisense oligonucleotide (20 pmol, 20 nl) designed to target a region of the c-fos mRNA that flanks the initiation codon (5'-129 to 143-3'). The same treatment also discernibly enhanced the BRR response, but elicited no appreciable effect on systemic arterial pressure or heart rate. On the other hand, bilateral application to the NTS of the corresponding sense oligonucleotide (20 pmol, 20 nl) or an antisense cDNA (20 pmol, 20 nl) that targeted a different site of the c-.fos mRNA (5'-135 to 149-3') was ineffective. These results suggest that expression of the inducible c-fos gene in the NTS may represent an early step in the cascade of intracellular events that leads to long-term inhibitory modulation of baroreflex control of blood pressure.

Animals↗

PubMed1996

Participation of endogenous galanin in the suppression of baroreceptor reflex response by locus coeruleus in the rat.

We evaluated the potential participation of endogenous brain galanin (GAL) in the suppression of baroreceptor reflex (BRR) response by locus coeruleus (LC), using adult male Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p., with 15 mg/kg/h i.v. infusion supplements). Our physiologic and pharmacologic results demonstrated that bilateral microinjection of GAL antiserum (1:20, 20 nl) into the nucleus tractus solitarii (NTS), the terminal site for baroreceptor afferent fibers, significantly attenuated the suppressive effect of LC on the BRR response. Pretreatment with the same amount of normal rabbit serum (1:20) or heat-inactivated GAL antiserum (1:20), on the other hand, was ineffective. Microinjection of GAL (100 pmol) into the bilateral NTS also appreciably depressed the BRR response. Histochemically, retrogradely labeled neurons were distributed in the LC following microinjection of fast blue into the NTS. Immunofluorescent staining further revealed that some of these fast blue labeled LC neurons also showed positive immunoreactivity to GAL. These results suggest that a direct galaninergic projection to the NTS may participate in the suppression of BRR response by the LC.

Amidines↗

PubMed1996

Inhibition of human DNA ligase I activity by zinc and cadmium and the fidelity of ligation.

Heavy metals, including zinc (Zn) and cadmium (Cd), are potentially important genotoxic agents in our environment. Here we report that human DNA ligase I, the major form of the enzyme in replicative cells, is a target for Zn and Cd ions. ZnCl2 at 0.8 mM caused complete inhibition of DNA ligase I activity, whereas only 0.04 mM CdCl2 was required to achieve a similar effect. Both metals affected all three steps of the reaction, namely, the formation of ligase-AMP intermediate, the transfer of the AMP to DNA and the ligation reaction that succeeds the formation of the AMP-DNA complex. Unlike F-ara-ATP and the natural protein inhibitor of DNA ligase-I, these metals may affect different domains of the enzyme. Moreover, these metal ions did not increase the rate of misligation of F-ara-A-modified DNA or mismatched DNA substrates, but considerable misligation was observed for the T:C mispairing. These data support the notion of high fidelity of the human DNA ligases and that the major action of these metal ions on the enzyme is their inhibitory function.

Adenosine Monophosphate↗

PubMed1996

Concurrent elicitation of electroencephalographic desynchronization and penile erection by cocaine in the rat.

It is well-known from animal and human studies that, as a central nervous stimulant, cocaine induces electroencephalographic (EEG) desynchronization. Cocaine also purportedly increases sexual behavior as an aphrodisiac. Whether the effects of cocaine on EEG activity and penile erection are mechanistically linked, however, remains to be fully elucidated. We evaluated whether this link exists, based on simultaneous recording of EEG signals from the somatosensory cortex and intracavernous pressure (ICP, as experimental index for penile erection) in adult, male Sprague-Dawley rats. Under intraperitoneal chloral hydrate anesthesia (400 mg/kg, i.p.), both intravenous (i.v.) and intracavernous (i.c.) administration of cocaine (1.5 or 3.0 mg/kg, and 75 or 150 micrograms) dose-dependently induced discernible EEG desynchronization, as represented by a decrease in root mean square and an increase in mean power frequency values, and an increase in ICP. However, the same administration of cocaine in animals under pentobarbital sodium anesthesia (50 mg/kg, i.p.) failed to significantly affect EEG activity, despite an appreciable dose-dependent elevation in ICP. On the other hand, intracerebroventricular administration of cocaine (7.5, 15, or 30 micrograms) induced significant EEG activation without affecting ICP. I.c. application of papaverine (400 micrograms) elicited a discernible increase in ICP, but failed to evoke EEG desynchronization. These results suggest that the concurrent EEG desynchronization and penile erection elicited by cocaine may take place without a mutually causative relationship.

Animals↗

PubMed1996

Identification of a cDNA encoding 6-phosphogluconate dehydrogenase from a human heart cDNA library.

A full-length cDNA clone for human 6-phosphogluconate dehydrogenase (PGD) was isolated from a human adult heart cDNA library. The clone encoded an open reading frame of 483 amino acids. When the amino acid sequences of human PGD and sheep PGD were aligned, 94.2% identity between these two proteins was found. Its calculated molecular weight is 53,149 daltons. The predicted isoelectric point is 6.85. When the secondary structure of human PGD was examined by the PROSIS software, 36% alpha-helix and 9% beta-sheet were found.

Adult↗

PubMed1996

Nitric oxide as a mediator of cocaine-induced penile erection in the rat.

1. The effect of local application of cocaine to the corpus cavernosum on intracavernous pressure (ICP), an experimental index for penile erection, was examined in Sprague-Dawley rats anaesthetized with chloral hydrate. The potential involvement of dopamine, noradrenaline or nitric oxide as the chemical mediator in this process, and the pharmacological action of cocaine as a local anaesthetic in the induced increase in ICP, were also investigated. 2. Intracavernous (i.c.) administration of cocaine (40, 80 or 160 micrograms) to the corpus cavernosum resulted in a dose-related increase in both amplitude and duration of ICP. 3. The elevation of ICP induced by cocaine (160 micrograms, i.c.) was not significantly influenced by prior injection into the corpus cavernosum of either the D1 or D2 dopamine receptor antagonist, R-(+)-SCH 22390 (250 pmol) or (-)-sulpiride (250 pmol). 4. Similarly, penile erection promoted by cocaine (160 micrograms, i.c.) was not appreciably affected by i.c. pretreatment with the alpha 1-, alpha 2-, or beta-adrenoceptor antagonist, prazosin (50 pmol), yohimbine (50 pmol) or propranolol (5 nmol). 5. Whereas lignocaine (4 mumol, i.c.) depressed penile erection induced by papaverine (400 micrograms, i.c.), local application of cocaine (160 micrograms) into the corpus cavernosum still elicited significant elevation in ICP in the presence of lignocaine or papaverine. 6. The increase in ICP induced by cocaine (160 micrograms, i.c.) was attenuated dose-dependently by prior cavernosal administration of the NO synthase inhibitor, N omega-nitro-L -arginine methyl ester (L-NAME, 0.5, 1 or 5 pmol) or NG-monomethyl-L-arginine (L-NMMA, 2.5, 5 or 10 pmol). The blunting effect of L-NAME or L-NMMA was reversed by co-administration of the NO precursor, L-arginine (1 nmol, i.c.). 7. Pretreatment by local application into the corpus cavernosum of methylene blue (2.5 mumol), an inhibitor of cytosolic guanylyl cyclase, antagonized cocaine-induced penile erection. 8. Direct i.c. administration of a NO donor, nitroglycerin (10 or 20 nmol), mimicked the local action of cocaine by promoting a significant increase in ICP. 9. It is concluded that cocaine may induce penile erection by increasing ICP via a local action on the corpus cavernosum. This process did not appear to involve either dopamine or noradrenaline as the chemical mediator, nor the pharmacological action of cocaine as a local anaesthetic. On the other hand, it is likely that initiation and maintenance of penile erection elicited by cavernosal application of cocaine engaged an active participation of NO and subsequent activation of guanylyl cyclase in the corpus cavernosum.

Anesthetics, Local↗

PubMed1996

Participation of galanin in baroreflex inhibition of heart rate by hypothalamic PVN in rat.

We investigated the role of galanin (Gal) in the suppression of baroreceptor reflex (BRR) response by the paraventricular nucleus of the hypothalamus (PVN) in adult male Sprague-Dawley rats that were anesthetized with pentobarbital sodium. Electrical stimulation (10-s train of 1-ms rectangular pulses at 20-40 microA and 10-20 Hz) of, and microinjection of L-glutamate (1 nmol) into, the PVN significantly inhibited BRR response to transient hypertension induced by phenylephrine (5 micrograms/kg iv). Such a PVN-induced BRR suppression was appreciably antagonized by local administration of Gal antiserum (1:20), but not heat-inactivated Gal antiserum (1:20), to the nucleus tractus solitarius (NTS) bilaterally. Microinjection of Gal (100 pmol) into the NTS bilaterally also resulted in a Gal antiserum-reversible inhibition of the BRR response. Immunohistochemical results demonstrated that the distribution of Gal-containing neurons in the parvocellular subnucleus of the PVN overlapped substantially with the hypothalamic loci on which electrical or chemical activation elicited suppression of the BRR response that was significantly blunted by microinjection of Gal antiserum into the NTS. These results suggest that the PVN may participate in central cardiovascular regulation by suppressing the BRR response via galaninergic neurotransmission at the NTS.

Animals↗

PubMed1995

Identification of a brain- and reproductive-organs-specific gene responsive to DNA damage and retinoic acid.

We have identified and sequenced a new gene from human cells that is responsive to DNA damage and retinoic acid treatment, and it is highly expressed in brain and reproductive organs (BRE). This BRE gene encodes an mRNA of 1.7-1.9 kb, with an open reading frame of 1,149 bp, and gives rise to a deduced polypeptide of 383 amino acid residues. Treatment of fibroblast cell with UV and 4-nitroquinoline-1-oxide caused more than 90% and 50% decreases in BRE mRNA, respectively. Similar decreases in BRE expression were observed in RA-treatment of the brain glioma cell U-251 and the promyelocytic cell HL-60. Decrease in BRE mRNA was also observed in a squamous carcinoma cell, 1483, that showed X-ray resistance and has a more aggressive tumorigenic phenotype, but BRE expression was unchanged in cells after growth inhibition. These data indicate that BRE is a house-keeping gene and it may play a role in homeostatis or in certain pathways of differentiation in cells of neural, epithelial and germ line origins.

Amino Acid Sequence↗

PubMed1995

Participation of presynaptic noradrenergic fibers in the suppression of alpha 2-adrenoceptor activity by substance P at the nucleus reticularis gigantocellularis of the rat.

We applied reverse microdialysis and high performance liquid chromatography (HPLC) analysis to evaluate the participation of presynaptic noradrenergic neurotransmission in the suppression by substance P (SP) of alpha 2-adrenoceptor activity at the nucleus reticularis gigantocellularis (NRGC) in Sprague-Dawley rats anesthetized with pentobarbital sodium. Microinfusion of SP (600 microM/min) into the NRGC through a stereotaxically positioned microdialysis probe attenuated the hypotensive and bradycardiac actions of the alpha 2-adrenoceptor agonist, guanabenz (100 micrograms/kg, i.v.). This inhibitory effect correlated positively with the time course of elevation in the estimated extracellular concentrations of SP and norepinephrine (NE) in the NRGC. Direct microinfusion of NE (50 nM/min) into the NRGC also lessened the cardiosuppressant effects of guanabenz. These circulatory and NE responses to SP were, however, significantly blunted in rats in which the noradrenergic innervation in the NRGC was depleted with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) pretreatment. Microinfusion of NE into the NRGC of DSP4-pretreated animals restored the attenuation of guanabenz-induced cardiovascular suppression. These results suggest that SP may depress the activity of alpha 2-adrenoceptor at the NRGC that are involved in circulatory regulation by increasing the extracellular concentration of NE via a presynaptic modulation of noradrenergic neurotransmission.

Adrenergic alpha-Antagonists↗

PubMed1995

Chromosomal localization of the human NF-E2 family of bZIP transcription factors by fluorescence in situ hybridization.

A family of human genes encoding basic-leucine zipper (bZIP) transcription factors, p45-NF-E2, Nrf1 and Nrf2, have been isolated independently. Whereas the encoded proteins of the three genes share highly conserved regions distinct from other bZIP families such as Jun or Fos, remaining regions diverged considerably from each other. Chromosomal localization by fluorescence in situ hybridization demonstrates that these genes are non-syntenic. p45-NF-E2 mapped to chromosome 12q13.1-13.3, whereas Nrf1 and 2 mapped to 17q21.3 and 2q31, respectively. However, these three genes were probably derived from a single ancestor by chromosomal duplication as other genes that also map in these regions are related to one another.

Amino Acid Sequence↗

PubMed1995

Excitatory innervation of caudal hypoglossal nucleus from nucleus reticularis gigantocellularis in the rat.

We examined the possible innervation of the caudal hypoglossal nucleus by the nucleus reticularis gigantocellularis of the medulla oblongata, based on single-neuron recording and retrograde tracing experiments in Sprague-Dawley rats. Under pentobarbital sodium (50 mg/kg, i.p.) anesthesia, electrical stimulation of the caudal portion of the nucleus reticularis gigantocellularis with repetitive 0.5-ms rectangular pulses increased (46 of 51 neurons) the basal discharge frequency of spontaneously active cells, or evoked spike activity in silent, hypoglossal neurons located at the level of the obex. This excitatory effect was related to the intensity (25-100 microA) and/or frequency (0.5-20 Hz) of the stimulating pulses to the nucleus reticularis gigantocellularis. Perikaryal activation of neurons by microinjection of L-glutamate (0.5 nmol, 25 nl) into the caudal portion of the nucleus reticularis gigantocellularis similarly produced an excitatory action on eight of 14 hypoglossal neurons. Retrogradely labeled neurons were found bilaterally within the confines of the nucleus reticularis gigantocellularis following unilateral microinjection of wheatgerm agglutinin-conjugated horseradish peroxidase or Fast Blue into the corresponding hypoglossal recording sites. Furthermore, the distribution of labeled neurons in the nucleus reticularis gigantocellularis substantially overlapped with the loci of electrical or chemical stimulation. These complementary electrophysiological and neuroanatomical results support the conclusion that an excitatory link exists between the nucleus reticularis gigantocellularis and at least the caudal portion of the hypoglossal nucleus in the rat.

Amidines↗

PubMed1995

Participation of noradrenergic neurotransmission in the enhancement of baroreceptor reflex response by substance P at the nucleus tractus solitarii of the rat: a reverse microdialysis study.

We applied reverse microdialysis and HPLC analysis to evaluate the participation of noradrenergic neurotransmission in modulation of the baroreceptor reflex response by substance P at the nucleus tractus solitarii in Sprague-Dawley rats anesthetized with pentobarbital sodium (50 mg/kg, i.p., with 20 mg/kg/h.i.v. supplement). Continuous infusion of substance P (600 microM) at 1 microliter/min into the nucleus tractus solitarii through a stereotaxically positioned microdialysis probe (active exchange length, 180-200 microns; diameter, 220 microns) for 1 h elicited an enhancement of the baroreceptor reflex response. This facilitatory effect correlated positively, during the 60-min infusion period, with the time course of increase in the extracellular concentration of substance P and noradrenaline in the nucleus tractus solitarii. Experimentally elevating the concentration of noradrenaline at this medullary nucleus also augmented the baroreceptor reflex sensitivity. On the other hand, depletion of the noradrenergic fibers and nerve terminals at the nucleus tractus solitarii with DSP4 diminished the enhancement of baroreceptor reflex response and the corresponding elevation in extracellular concentration of noradrenaline by substance P. Microinfusion of noradrenaline into the nucleus tractus solitarii in DSP4-treated animals, however, potentiated the baroreceptor reflex response. These results suggested that the enhancement of baroreceptor reflex response by substance P may involve an increase in the concentration of noradrenaline at the nucleus tractus solitarii via a presynaptic mechanism.

Animals↗

PubMed1995

Participation of hypothalamic paraventricular nucleus in locus ceruleus-induced baroreflex suppression in rats.

We evaluated the potential role of the paraventricular nucleus (PVN) of the hypothalamus in the suppression of baroreceptor reflex (BRR) response by locus ceruleus (LC), using adult male Sprague-Dawley rats anesthetized with pentobarbital sodium. Electrical stimulation of histologically verified sites in the LC elicited significant reduction in the BRR response. This suppressive effect of LC on BRR response was appreciably antagonized by bilateral electrolytic lesions of the PVN and reversibly blocked by bilateral microinjection of 2% lidocaine into similar hypothalamic loci. Local administration of the alpha 1-adrenoceptor antagonist, prazosin (50 pmol), or an antiserum directed against neuropeptide Y (NPY) (1:20) into the bilateral PVN also significantly attenuated the suppression elicited by LC on BRR response. In contrast, treatments with the alpha 2-adrenoceptor blocker, yohimbine (50 pmol), heat-inactivated NPY antiserum (1:20), artificial cerebrospinal fluid, or normal rabbit serum (1:20) produced no discernible effect. These results suggest that the PVN may constitute part of the efferent pathways through which LC elicits its inhibition on the BRR response. Furthermore, LC may activate this pathway via alpha 1-adrenoceptors and NPY receptors in the PVN.

Adrenergic alpha-Antagonists↗

PubMed1995

Central effect of angiotensin III on caudal hypoglossal neurons in rats.

We communicated the central effect of angiotensin III (ANG III), a potent signal for extracellular dehydration, on single neurons in the caudal hypoglossal nucleus of Sprague-Dawley rats anesthetized with pentobarbital sodium. A significant number (121 of 168) of caudal hypoglossal neurons responded to intracerebroventricular application of ANG III (80 or 160 pmol), with either an increase (n = 83) or decrease (n = 38) in their spontaneous discharge. These effects of ANG III were significantly reversed by intracerebroventricular application of the nonpeptide angiotensin AT1 receptor antagonist losartan (40 nmol), but not by the AT2 antagonist, PD-123319. The hypoglossal neuronal responses to repeated administration of ANG III (80 pmol), delivered at an interval < or = 18 min, exhibited acute tachyphylaxis. Intracerebroventricular administration of the cholinergic dipsogen, carbachol (50 ng), or the osmotic stimulant, hypertonic saline (0.5 M), also elicited responses in ANG III-responsive hypoglossal neurons. These results suggest that neurons in the caudal hypoglossal nucleus may serve as the final common pathway for extracellular and, possibly, intracellular thirst in the rat. Furthermore, it is likely that the action of ANG III is mediated by the AT1 subtype of angiotensin receptors.

Angiotensin III↗

PubMed1994

Participation of noradrenergic neurotransmission in the suppression by substance P of alpha 2-adrenoceptors at the nucleus reticularis gigantocellularis involved in central cardiovascular regulation in the rat.

We applied reverse microdialysis and HPLC analysis to quantify the participation of noradrenergic neurotransmission in the modulation by substance P of alpha 2-adrenoceptors at the nucleus reticularis gigantocellularis involved in cardiovascular regulation, using Sprague-Dawley rats anesthetized with pentobarbital sodium. The efficacy of circulatory suppression of a centrally acting alpha 2-adrenoceptor agonist, guanabenz, was used as the experimental index. Continuous infusion of substance P (600 or 1200 pmol/microliters/min) into the nucleus reticularis gigantocellularis through a stereotaxically positioned microdialysis probe (active exchange length: 500 microns, diameter: 220 microns) for 80 min elicited a reduction in the hypotensive and bradycardiac actions of guanabenz (100 micrograms/kg, i.v.). This implied suppression of alpha 2-adrenoceptor activity correlated positively with the time-course of increase in the estimated extracellular concentration of the undecapeptide and norepinephrine in the nucleus reticularis gigantocellularis. Experimentally elevating the concentration of norepinephrine at this reticular nucleus via microinfusion by reverse microdialysis also decreased the efficacy of the cardiovascular suppression of the aminoguanidine compound. These results suggest that substance P may depress the activity of the alpha 2-adrenoceptors in the nucleus reticularis gigantocellularis that are involved in central cardiovascular regulation via an increase in the extracellular concentration of norepinephrine at this reticular nucleus.

Adrenergic alpha-Antagonists↗

PubMed1994

Characterization and application of microdialysis probes with an active exchange length compatible with small-size brain nuclei in the rat.

We communicated the construction, characterization and application of microdialysis probes with an active exchange length that is suitable for experiments involving small-size nuclei in rat brain. Using substance P (SP) as the test substance, we determined that probes with an active exchange length of 180-200 microns exhibited an in vitro recovery of 14.2 +/- 0.8% and in vivo recovery at the nucleus tractus solitarii (NTS) of 24.9 +/- 1.7% for the undecapeptide, calibrated at an infusion rate of 1 microliter/min. We also demonstrated that microinfusion of SP via these probes into the NTS allowed for a correlation of changes in tissue levels of both SP (exogenous substance) and norepinephrine (endogenous substance) with alterations in baroreceptor reflex responses (physiologic phenomenon).

Animals↗

PubMed1994

Modulation by angiotensin III of nociception-related and arterial pressure-related neuronal responsiveness in the nucleus reticularis gigantocellularis of the rat.

We evaluated possible modulation by angiotensin III (AIII) of the interactive effect of noxious stimuli and elevation in systemic arterial pressure on the responsiveness of neurons in the nucleus reticularis gigantocellularis (NRGC) of the medulla oblongata. Combined extracellular single-neuron recording and microiontophoresis were carried out on male, adult Sprague-Dawley rats anesthetized with pentobarbital sodium. The responsiveness of NRGC neurons to nociception (tail clamp) and/or transient hypertension elicited by phenylephrine (5 micrograms/kg, i.v.), in the absence or presence of AIII, was used as the experimental index. Microiontophoretic application of the heptapeptide suppressed the responses of spontaneously active NRGC neurons to individually delivered nociception or hypertension. Interestingly, the preferential reduction in responsiveness to tail clamp upon simultaneous elevation in arterial pressure was reversed to one that favored nociception in the presence of AIII. These actions of the heptapeptide appeared to be receptor-specific, since they were discernibly blocked by its selective antagonist, Ile7-angiotensin III. Our results reveal that neuropeptides such as AIII may differentially modulate neuronal responsiveness according to the prevailing physiologic input(s) to the central nervous system of the animal.

Angiotensin III↗