Responses of Dorsal Horn Neurons to Peripheral Chemical Stimulation in the Spinal Cord of Anesthetized Cats

Sung Jun Jung,Joo Min Park,Joon Ho Lee,Ji Hye Lee,Su-Yong Eun,Sang Jeong Kim,Won-Il Lim,Sun Hee Cho,Jun Kim 대한생리학회-대한약리학회 2000 The Korean Journal of Physiology & Pharmacology Vol.4 No.1

<P> Although nociceptive informations are thought to be processed via different neural mechanisms depending on the types of stimuli, sufficient data have not been accumulated yet. We performed a series of experiments to elucidate the possible neural mechanisms as to chemical stimuli such as formalin, capsaicin and ATP. <P>Single unit activity of wide dynamic range (WDR) neurons and high threshold cells were recorded extracellularly from the lumbosacral enlargement of cat spinal cord before and after chemical stimulation to its receptive field (RF). Each chemical substance - formalin (20μl, 4%), capsaicin (33 mM) or Mg-ATP (5 mM)- was injected intradermally into the RFs and then the changes in the spontaneous activity, mechanical threshold and responses to the peripheral mechanical stimuli were observed. In many cases, intradermal injection of formalin (5/11) and capsaicin (8/11) resulted in increase of the spontaneous activity with a biphasic pattern, whereas ATP (8/8) only showed initial responses. Time courses of the biphasic pattern, especially the late response, differed between formalin and capsaicin experiments. One hour after injection of each chemical (formalin, capsaicin, or ATP), the responses of the dorsal horn neurons to mechanical stimuli increased at large and the RFs were expended, suggesting development of hypersensitization (formalin 6/10, capsaicin 8/11, and ATP 15/19, respectively). These results are suggested that formalin stimulates peripheral nociceptor, local inflammation and involvement of central sensitization, capsaicin induces central sensitization as well as affects the peripheral C-polymodal nociceptors and neurogenic inflammation, and ATP directly stimulates peripheral nociceptors.

Regulation of Phosphorylated cAMP Response Element-Binding Protein, Fos-Related Antigen and FosB Expression by Dopamine Agonists in Rat Striatum

Eun Sang Choe,Jong Yeon Kim 대한생리학회-대한약리학회 2001 The Korean Journal of Physiology & Pharmacology Vol.5 No.4

<P> Activation of D1-like dopamine receptors by psychostimulants, such as amphetamine, upregulates the expression of immediate early gene and opioid peptide gene in the striatum. The genomic changes are regulated by phosphorylated transcription factors via complicated intracellular events. To evaluate temporal expression of the transcription factors by dopaminergic stimulation, the D1-like dopamine agonist, amphetamine or SKF82958, was systematically delivered. As intracellular markers in response to the agonist, phosphorylated cAMP response element-binding protein (pCREB), Fos-related antigens (FRA) and FosB immunoreactivity (IR) was compared at 20 and 120 min time points in the selected areas of the striatum. Semi-quantitative immunocytochemistry showed that amphetamine (5 mg/kg, i.p.) significantly increased pCREB-IR at 20 min, sustained up to 60 min and decreased at 120 min after the infusion. Like amphetamine, the full D1 agonist, SKF82958 (0.5 mg/kg, s.c.), also increased pCREB-IR at 20 min, but not at 120 min after the infusion in the dorsal striatum (caudoputaman, CPu) and shell of ventral striatum (nucleus accumbens, NAc). In contrast, FRA- and FosB-IR induced by SKF82958 was significantly increased at 120 min, but not at 20 min after the administration. These data indicate that SKF82958 mimics induction of CREB phosphorylation by amphetamine and differentially regulates temporal induction of pCREB, and FRA and FosB expression in the striatum.

Interaction of genetic background and exercise training intensity on endothelial function in mouse aorta

Seung Kyum Kim,Joshua J,Avila,Michael P,Massett 대한생리학회-대한약리학회 2020 The Korean Journal of Physiology & Pharmacology Vol.24 No.1

The purpose of this study was to characterize the genetic contribution to endothelial adaptation to exercise training. Vasoreactivity was assessed in aortas from four inbred mouse strains (129S1, B6, NON, and SJL) after 4 weeks of moderate intensity continuous exercise training (MOD), high intensity interval training (HIT) or in sedentary controls (SED). Intrinsic variations in endothelium-dependent vasorelaxation (EDR) to acetylcholine (ACh) as well as vasocontractile responses were observed across SED groups. For responses to exercise training, there was a significant interaction between mouse strain and training intensity on EDR. Exercise training had no effect on EDR in aortas from 129S1 and B6 mice. In NON, EDR was improved in aortas from MOD and HIT compared with respective SED, accompanied by diminished responses to PE in those groups. Interestingly, EDR was impaired in aorta from SJL HIT compared with SED. The transcriptional activation of endothelial genes was also influenced by the interaction between mouse strain and training intensity. The number of genes altered by HIT was greater than MOD, and there was little overlap between genes altered by HIT and MOD. HIT was associated with gene pathways for inflammatory responses. NON MOD genes showed enrichment for vessel growth pathways. These findings indicate that exercise training has non-uniform effects on endothelial function and transcriptional activation of endothelial genes depending on the interaction between genetic background and training intensity.

Synergistic Induction of iNOS by IFN-g and Glycoprotein Isolated from Dioscorea batatas

Pham Thi Thu Huong,Min Young Lee,Kun Yeong Lee,In Youp Chang,Seog Ki Lee,Sang Pil Yoon,Dong-Cheol Lee,Young Jin Jeon 대한생리학회-대한약리학회 2012 The Korean Journal of Physiology & Pharmacology Vol.16 No.6

Dioscorea species continue to be used in traditional Chinese medicine, and represent a major source of steroid precursors for conventional medicine. In the previous study, We isolated glycoprotein (GDB) from Dioscorea batatas, characterized, and demonstrated immunostimulating activity in C57BL/6 mice. The aim of this study was to investigate the mechanism whereby GDB activates macrophages. Macrophages activation by GDB was investigated by analyzing the effects of GDB on nitric oxide (NO) production, iNOS expression, mitogen activated protein kinase (MAPK) phosphorylation, and transcription factor activation. In the presence of IFN-Ճ, GDB strongly stimulated macrophages to express iNOS and produce NO. Furthermore, the activation of p38 was synergistically induced by GDB plus IFN-Ճ, but SB203580 (a p38 inhibitor) inhibited GDB plus IFN-Ճ-induced p38 activation. This study indicates that GDB is an important activator of macrophages. Furthermore, due to the critical role that macrophage activation plays in innate immune response, the activation effects of GDB on macrophages suggest that GDB may be a useful immunopotentiating agent.

Altered Cerebral Vasomotion with Decreased CGRP Level in Pial Arteries of Spontaneously Hypertensive Rats

Kwang Ho Lee,Jae Moon Choi,Ki Whan Hong 대한생리학회-대한약리학회 1998 The Korean Journal of Physiology & Pharmacology Vol.2 No.5

<P> The study aims to identify the mechanism (s) underlying the altered vasodilatory responses of the pial artery of spontaneously hypertensive rats (SHR) under a hypothesis that calcitonin gene-related peptide (CGRP) exerts a modulator role in the autoregulation of cerebral blood flow (CBF). The animals were divided into four groups: 1) Sprague-Dawley rats (SDR), 2) Wistar rats (WR), 3) SHR with high blood pressure (BP≥150 mmHg), and 4) SHR with normotensive BP (≤150 mmHg). The lower limit of CBF autoregulation in SHR shifted to a higher BP (82.8⁑9.3 mmHg, <I>P</I><0.05) than that in SDR (58.9⁑5.7 mmHg). In SHR, whether the BP levels were high or normotensive, the vasodilator responses to a stepwise hypotension were significantly attenuated unlike with SDR and WR. When artificial cerebrospinal fluid (CSF) containing capsaicin (3⁓10<SUP>-7</SUP> M) was suffused over the cortical surface, a transient increase in pial arterial diameter was observed in the SHR with high or normotensive BP. In contrast, SDR and WR showed a large increase in diameter, and the increase was sustained for over 10 minutes. In line with these results, the basal releases of CGRP-like immunoreactivity (CGRP-LI) in the isolated pial arteries from SHR with high and normotensive BP were 12.5⁑1.4 and 9.8⁑2.8 fmole/mm<SUP>2</SUP>/60 min (<I>P</I><0.05), while those from SDR and WR were 25.5⁑3.1 and 24.6⁑3.1 fmole/mm<SUP>2</SUP>/60 min, respectively. The isolated basilar arteries showed similar results to those of the pial arteries in SHR. Thus, it is summarized that, in the SHR, the reduced autoregulatory vasodilator responses to stepwise hypotension and capsaicin may be, in part, ascribed to the decreased release of CGRP from the perivascular sensory nerve fibers of the pial arteries, and that altered vasomotor activity in SHR may not be related with the hypertensive tone.

4-(Tert-butyl)-2,6-bis(1-phenylethyl)phenol induces pro-apoptotic activity

Jun Ho Kim,Yunmi Lee,Mi-Yeon Kim,Jae Youl Cho 대한생리학회-대한약리학회 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.3

Previously, we found that KTH-13 isolated from the butanol fraction of <i>Cordyceps bassiana </i>(Cb-BF) displayed anti-cancer activity. To improve its anti-proliferative activity and production yield, we employed a total synthetic approach and derivatized KTH-13 to obtain chemical analogs. In this study, one KTH-13 derivative, 4-(tert-butyl)-2,6-bis(1-phenylethyl)phenol (KTH-13-t-Bu), was selected to test its anti-cancer activity. KTH-13-t-Bu diminished the proliferation of C6 glioma, MDA-MB-231, LoVo, and HCT-15 cells. KTH-13-t-Bu induced morphological changes in C6 glioma cells in a dose-dependent manner. KTH-13-t-Bu also increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, KTH-13-t-Bu increased the levels of cleaved caspase-3 and -9. In contrast, KTH-13-t-Bu upregulated the levels of pro- and cleaved forms of caspase-3, -8, and -9 and Bcl-2. Phospho-STAT3, phospho-Src, and phospho-AKT levels were also diminished by KTH13-t-Bu treatment. Therefore, these results strongly suggest that KTH-13-t-Bu can be considered a novel anti-cancer drug displaying pro-apoptotic activity.

Characterization of Norepinephrine Release in Rat Posterior Hypothalamus Using<I> in vivo</I> Brain Microdialysis

Ki-Wug Sung,Seong Yun Kim,Ok Nyu Kim,Sang Bok Lee 대한생리학회-대한약리학회 2002 The Korean Journal of Physiology & Pharmacology Vol.6 No.1

<P> In the present study, we used the microdialysis technique combined with high performance liquid chromatography (HPLC) and electrochemical detection to measure the extracellular levels of norepinephrine (NE) in the posterior hypothalamus <I>in vivo</I>, and to examine the effects of various drugs, affecting central noradrenergic transmission, on the extracellular concentration of NE in the posterior hypothalamus. Microdialysis probes were implanted stereotaxically into the posterior hypothalamus (coordinates: posterior 4.3 mm, lateral 0.5 mm, ventral 8 mm, relative to bregma and the brain surface, respectively) of rats, and dialysate collection began 2 hr after the implantation. The baseline level of monoamines in the dialysates were determined to be: NE 0.17⁑0.01, 3,4-dihydroxyphenylacetic acid (DOPAC) 0.94⁑0.07, homovanillic acid (HVA) 0.57⁑0.05 pmol/sample (n=8). When the posterior hypothalamus was perfused with 90 mM potassium, maximum 555% increase of NE output was observed. Concomitantly, this treatment significantly decreased the output of DOPAC and HVA by 35% and 28%, respectively. Local application of imipramine (50μM) enhanced the level of NE in the posterior hypothalamus (maximum 200%) compared to preperfusion control values. But, DOPAC and HVA outputs remained unchanged. Pargyline, an irreversible monoamine oxidase inhibitor, i.p. administered at a dose of 75 mg/kg, increased NE output (maximum 165%), while decreased DOPAC and HVA outputs (maximum 13 and 12%, respectively). These results indicate that NE in dialysate from the rat posterior hypothalamus were neuronal origin, and that manipulations which profoundly affected the levels of extracellular neurotransmitter had also effects on metabolite levels.

Involvement of Caspases and Bcl-2 Family in Nitric Oxide-Induced Apoptosis of Rat PC12 Cells

Yeon-Jin Jeong,Ji-Yeon Jung,Jin-Ha Lee,Jin-Hyoung Cho,Guem-Sug Lee,Sun-Hun Kim,Won-Jae Kim 대한생리학회-대한약리학회 2006 The Korean Journal of Physiology & Pharmacology Vol.10 No.6

This study was aimed to investigate the nitric oxide (NO)-induced cytotoxic mechanism in PC12 cells. Sodium nitroprusside (SNP), an NO donor, decreased the viability of PC12 cells in dose- and time- dependent manners. SNP enhanced the production of reactive oxygen species (ROS), and gave rise to apoptotic morphological changes including cell shrinkage, chromatin condensation, and DNA fragmentation. Expression of Bax was not affected, whereas Bcl-2 was downregulated in SNP-treated PC12 cells. SNP augmented the release of cytochrome c from mitochondria into cytosol and enhanced caspase ⁣8, ⁣9, and ⁣3 activities. SNP upregulated both Fas and Fas-L, which are known to be components of death receptor assembly. These results suggest that NO induces apoptosis of PC12 cells through both mitochondria- and death receptor-mediated pathways mediated by ROS and Bcl-2 family.

Congenital LQT Syndromes From Gene to Torsade de Pointes

Edward Carmeliet 대한생리학회-대한약리학회 2002 The Korean Journal of Physiology & Pharmacology Vol.6 No.1

<P> Congenital Long QT syndrome (LQTs) is a relatively rare pathologic disorder but results frequently in sudden cardiac death. Of the six LQTs that have been clinically described, five have been worked out for their genetic and biophysical profile. Most are generated by mutations which cause a loss of function in two delayed K<SUP>⁢</SUP>currents, i<SUB>Ks</SUB> and i<SUB>Kr</SUB>. One syndrome is generated by mutations in the Na<SUP>⁢</SUP> channel which causes essentially a gain of function in the channel. Clinically the syndromes are characterized by slowed repolarization of the cardiac ventricular action potential and the occurrence oftypical arrhythmias with undulating peaks in the electrocardiogram, called Torsade de Pointes. Arrhythmias are initiated by early or delayed afterdepolarizations and continue as reentry. Triggers for cardiac events are exercise (swimming; LQT1), emotion (arousal; LQT2) and rest/sleep (LQT3). β-blockers have a high efficacy in the treatment of LQT1 and LQT2. In LQT3 their use is questionable. The study of congenital LQTsyndromes is a remarkable example of how basic and clinical science converge and take profit of each other s contribution.

Gradual Reperfusion Lowers the Incidence of Reperfusion-Induced Ventricular Fibrillation in a Cat Model of Regional Ischemia

You-Ho Kim,Heung Sik Na,Hyun Jung Nam,Gyu-Young Hur,Seung-Whan Lee,Sung Sook Park,Seung Kil Hong 대한생리학회-대한약리학회 1999 The Korean Journal of Physiology & Pharmacology Vol.3 No.1

<P> Blood flow restoration to ischemic zone of the heart is essential to salvage of ischemic tissue. However, there is a large body of evidence documenting that the reperfusion can induce reperfusion injury like reperfusion-induced malignant arrhythmias. In the present study, employing a cat model of regional cardiac ischemia, we examined if reperfusion rendered in a gradual fashion could lower the incidence of reperfusion-induced ventricular fibrillation (VF), which usually precipitated within a few to several tens of seconds after abrupt reperfusion. The experiments were conducted with male mongrel cats (n=46, 2.5-5 kg). The animals in the control and 30 MIN groups were subjected to an episode of 20- and 30-min left anterior descending coronary artery occlusion, respectively, followed by abrupt reperfusion. The animals in 5 G and 10 G groups received gradual reperfusion over a 5- and 10-min period, respectively, following a 20-min occlusion. The proportion of animals that exhibited VF during the reperfusion phase was 11/15 in the control, 7/10 in the 30 MIN, 5/10 in the 5 G and 2/11 in the 10 G groups. The incidence of VF in the 10 G group was significantly lower than that in the control or 30 MIN group subjected to abrupt reperfusion. These results suggest that the gradual reperfusion is a useful procedure against reperfusion-induced VF.