• Journal of Life Science
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• v.11 no.1
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• pp.1-7
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• 2001

The caffeine intake cause a local or wide ranges of convulsion and it is associated with release of dopamine (DA) receptors into the brain striatum. However, the effect of caffeine addiction on expression of DA receptors gene in the rat caudate-putamen (CPu), nucleus accumbens (NAc), and olfactory tubercle (OTu) has not been elucidated. In this study, we examined the influence of caffeine addiction on DA D $_1$and D$_2$receptor mRNAs after the treatment of caffeine for four weeks. Using the specific antisense ribo-probes for DA D$_1$and D$_2$receptor cDNAs, in situ hybridization was performed on the CPu, NAc, and OTu of the adult male Sprague Dawely rats. In caffeine-treated group, DA D$_1$and D$_2$receptor mRNAs were highly increased in CPu, NAc, and OTu. The expression density of DA D$_1$receptor mRNAs were 2.52${\pm}$1.40 (CPu), 2.78${\pm}$1.69 (NAc), and 3.91${\pm}$1.28 (OTu) in control group and 7.76${\pm}$2.09 (CPu), 4.2 ${\pm}$1.85 (NAc), and 8.21${\pm}$1.72 (OTu) in caffeine-treated group. The expression density of DA D$_2$receptor mRNA was 2.32${\pm}$1.52 (CPu), 2.63${\pm}$2.11 (NAc), and 3.61${\pm}$1.43 (OTu) in control group, and 6.41${\pm}$1.82 (CPu), 6.89${\pm}$1.32 (NAc), and 6.82${\pm}$1.18 (OTu) in caffeine-treated group. DA D$_1$receptor mRNA was higher expressed than DA D$_2$ receptor mRNA in CPu and NAc. These results suggest that caffeine reacts as a upregulator of the expression of DA D$_1$and D$_2$receptor mRNA among the neurotransmitters.

• Biomolecules & Therapeutics
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• v.17 no.1
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• pp.32-42
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• 2009

The purpose of the present study was to examine the effect of dihydrexidine, a full $D_1$ receptor agonist, on the secretion of catecholamines (CA) from the perfused model of the rat adrenal gland, and to establish its mechanism of action. Dihydrexidine (10-100 ${\mu}M$), perfused into an adrenal vein for 60 min, relatively produced dose- and time-dependent inhibition in the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Dihydrexidine itself did fail to affect basal CA output. Also, in adrenal glands loaded with dihydrexidine (30 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$), an activator of L-type $Ca^{2+}$ channels, cyclopiazonic acid (10 ${\mu}M$), an inhibitor of cytoplasmic $Ca^{2+}$-ATPase, and veratridine, an activator of voltage-dependent $Na+$ channels (10 ${\mu}M$), were also markedly inhibited, respectively. However, in the simultaneous presence of dihydrexidine (30 ${\mu}M$) and R (+)-SCH23390 (a selective antagonist of $D_1$ receptor, 3 ${\mu}M$), the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644, cyclopiazonic acid and veratridine were considerably recovered to the extent of the corresponding control secretion compared with the inhibitory responses by dihydrexidinetreatment alone. In conclusion, these experimental results suggest that dihydrexidine significantly inhibits the CA secretion evoked by cholinergic stimulation (both nicotinic and muscarinic receptors) and membrane depolarization from the rat adrenal medulla. It seems that this inhibitory effect of dihydrexidine may be mediated by inhibiting influx of both $Ca^{2+}$ and $Na^+$ into the cytoplasm as well as by suppression of $Ca^{2+}$ release from cytoplasmic calcium store through activation of dopaminergic $D_1$ receptors located on the rat adrenomedullary chromaffin cells.

• The Journal of Korean Medicine
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• v.24 no.3
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• pp.72-83
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• 2003

Objective : The goal of the present study was to investigate the protective effect of Gamiheechum-tang (Jiaweixiqian-tang; GHCT) on brain tissue damage from chemical or ischemic insults. Methods : Levels of cultured cortical neuron death caused by toxic chemicals were measured by LDH release assay. Neuroprotective effects of GHCT on brain tissues were examined in vivo by ischemic model of middle cerebral artery (MCA) occlusion. Results : Animal groups treated with GBCT showed significantly decreased hypertension, and reduced levels of aldosterone, dopamine, and epinephrine in the plasma. GHCT treatments ($l0-200\mu\textrm{g}/ml$) significantly decreased cultured cortical neuron death mediated by AMPA, kainate, BSO, or Fe2+ when measured by LDH release assay. Yet, cell death mediated by NMDA was effectively protected by GHCT at the highest concentration examined ($200\mu\textrm{g}/ml$). In the in vivo experiment examining brain damage by MCA occlusion, affected brain areas by ischemic damage and edema were significantly less in animal groups administered with GHCT compared to the non-treated control group. Neurological examinations of forelimbs and hindlimbs showed that GHCT treatment improved animals' recovery from ischemic injury. Moreover, the extent of injury in cortical and hippocampal pyramidal neurons in ischemic rats was much reduced by GHCT, whose morphological features were similarly observed in non-ischemic animals. Conclusion : The present data suggest that GBCT may play an important role in protecting brain tissues from chemical or ischemic injuries.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.5
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• pp.197-206
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• 2007

The aim of the present study was to investigate the effects of 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine(SKF81297), a selective agonist of dopaminergic $D_1$ receptor, on the secretion of catecholamines(CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused rat adrenal gland, and also to elucidate the mechanism involved. SKF81297($10{\sim}100{\mu}M$) perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition of CA secretory responses evoked by ACh(5.32 mM), high $K^+$(56 mM), DMPP($100{\mu}M$) and McN-A-343($100{\mu}M$). Also, in adrenal glands loaded with SKF81297($30{\mu}M$), the CA secretory responses evoked by Bay-K-8644($10{\mu}M$), an activator of L-type $Ca^{2+}$ channels and cyclopiazonic acid($10{\mu}M$), an inhibitor of cytoplasmic $Ca^{2+}$-ATPase were also inhibited. However, in the presence of the dopamine $D_1$ receptor antagonist, (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-benzazepine-7-ol(SCH23390, $3{\mu}M$), which is a selective antagonist of dopaminergic $D_1$ receptor, the inhibitory responses of SKF81297($30{\mu}M$) on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644, and cyclopiazonic acid were significantly reduced. Collectively, these experimental results suggest that SKF81297 inhibits the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation(both nicotininc and muscarinic receptors) and membrane depolarization. This inhibitory of SKF81297 seems to be mediated by stimulation of dopaminergic $D_1$ receptors located on the rat adrenomedullary chromaffin cells, which are relevant to extra- and intracellular calcium mobilization. Therefore, it is thought that the presence of the dopaminergic $D_1$ receptors may be involved in regulation of CA release in the rat adrenal medulla.

• The Journal of Advanced Prosthodontics
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• v.3 no.3
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• pp.145-151
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• 2011

PURPOSE. This study was performed to investigate the ability of recombinant human-bone morphogenic protein-2 immobilized on a heparin-grafted bone substrate to enhance the osteoblastic functions. MATERIALS AND METHODS. The Bio-$Oss^{(R)}$, not coated with any material, was used as a control group. In rhBMP-2-Bio-$Oss^{(R)}$ group, rhBMP-2 was coated with Bio-$Oss^{(R)}$ using only deep and dry methods (50 ng/mL, 24 h). In heparinized rhBMP-2-Bio-$Oss^{(R)}$ group, dopamine was anchored to the surface of Bio-$Oss^{(R)}$, and coated with heparin. rhBMP-2 was immobilized onto the heparinized- Bio-$Oss^{(R)}$ surface. The release kinetics of the rhBMP-2-Bio-$Oss^{(R)}$ and heparinized rhBMP-2-Bio-$Oss^{(R)}$ were analyzed using an enzyme-linked immunosorbent assay. The biological activities of the MG63 cells on the three groups were investigated via cytotoxicity assay, cell proliferation assay, alkaline phosphatase (ALP) measurement, and calcium deposition determination. Statistical comparisons were carried out by one-way ANOVA test. Differences were considered statistically significant at $^*$P<.05 and $^{**}$P<.001. RESULTS. The heparinized rhBMP-2-Bio-$Oss^{(R)}$ showed more sustained release compared to the rhBMP-2-Bio-$Oss^{(R)}$ over an extended time. In the measurement of the ALP activity, the heparinized group showed a significantly higher ALP activity when compared with the non-heparinized groups (P<.05). The MG63 cells cultivated in the group with rhBMP-2 showed increased calcium deposition, and the MG63 cells from the heparinized group increased more than those that were cultivated in the non-heparinized groups. CONCLUSION. Heparin increased the rhBMP-2 release amount and made sustained release possible, and heparinized Bio-$Oss^{(R)}$ with rhBMP-2 successfully improved the osteoblastic functions.

• The Korean Journal of Nuclear Medicine
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• v.39 no.6
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• pp.413-420
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• 2005

Purpose: Neuroreceptor PET studies require 60-120 minutes to complete and head motion of the subject during the PET scan increases the uncertainty in measured activity. In this study, we investigated the effects of the data-driven head mutton correction on the evaluation of endogenous dopamine release (DAR) in the striatum during the motor task which might have caused significant head motion artifact. Materials and Methods: $[^{11}C]raclopride$ PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a monetary reward for 40 min. Dynamic frames acquired during the equilibrium condition (pre-task: 30-50 min, task: 70-90 min, post-task: 110-120 min) were realigned to the first frame in pre-task condition. Intra-condition registrations between the frames were performed, and average image for each condition was created and registered to the pre-task image (inter-condition registration). Pre-task PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the others. Volumes of interest (VOI) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DAR was calculated as the percent change of BP during and after the task. SPM analyses on the BP parametric images were also performed to explore the regional difference in the effects of head motion on BP and DAR estimation. Results: Changes in position and orientation of the striatum during the PET scans were observed before the head motion correction. BP values at pre-task condition were not changed significantly after the intra-condition registration. However, the BP values during and after the task and DAR were significantly changed after the correction. SPM analysis also showed that the extent and significance of the BP differences were significantly changed by the head motion correction and such changes were prominent in periphery of the striatum. Conclusion: The results suggest that misalignment of MRI-based VOI and the striatum in PET images and incorrect DAR estimation due to the head motion during the PET activation study were significant, but could be remedied by the data-driven head motion correction.

• The Journal of Pediatrics of Korean Medicine
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• v.20 no.1
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• pp.137-149
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• 2006

Objective : The purpose of this study is to investigate the effect of Radix Scutellariae on repeated nicotine-induced locomotor activity and c-Fos expression utilizing Fos-like immuno-histochemistry method in the nucleus accumbens, and the striatum, one of the major projection areas of the control DA system. Methods : Male Sprague-Dawley rats were divided into untreated(normal), nicotine-treated (control), Radix Scutellariae-treated(sample) groups, RS group received Radix Scutellariae(100mg/kg, i.p.) 30minutes before injection of nicotine(0.4mg/kg, s.c.) for 7days. Rat were followed withdrawal for 3 days and one challenge for 1day. Results : Systemic challenge with nicotine produced a much larger locomotor activity and expression of c-Fos in the nucleus accumbens and the striatum. Pretreatment with Radix Scutellariae decreased in nicotine-induced locomotor activity and c-Fos expression in the core, shell, straitum area. Conclusion : These results demonstrated that reduction in locomotor activity by Radix Scutellariae may be mediated by reduction of dopamine release and of postsynaptic neuronal activity in striatum, the nucleus accumbens. Out results show neurochemical evidence for the biological effects of Radix Scutellariae that ultimately may help us to understand how Radix Scutellariae can be used to treat nicotine addiction.

• BMB Reports
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• v.49 no.1
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• pp.1-2
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• 2016

Of the numerous events that occur in daily life, we readily remember salient information, but do not retain most less-salient events for a prolonged period. Although some of the episodes contain putatively emotional aspects, the information with lower saliency is rarely stored in neural circuits via an unknown mechanism. We provided substantial evidence indicating that synaptic plasticity in the dorsal ITC of amygdala allows for selective storage of salient emotional experiences, while it deters less-salient experience from entering long-term memory. After activation of D4R or weak fear conditioning, STDP stimulation induces LTD in the LA-ITC synapses. This form of LTD is dependent upon presynaptic D4R, and is likely to result from enhancement of GABA release. Both optogenetic abrogation of LTD and ablation of D4R at the dorsal ITC in vivo lead to heightened and over-generalized fear responses. Finally, we demonstrated that LTD was impaired at the dorsal ITC of PTSD model mice, which suggests that maladaptation of GABAergic signaling and the resultant LTD impairment contribute to the endophenotypes of PTSD. [BMB Reports 2016; 49(1): 1-2]

• Journal of Yeungnam Medical Science
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• v.40 no.4
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• pp.435-441
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• 2023

Pheochromocytomas and paragangliomas (PPGLs) may secrete hormones or bioactive neuropeptides such as interleukin-6 (IL-6), which can mask the clinical manifestations of catecholamine hypersecretion. We report the case of a patient with delayed diagnosis of paraganglioma due to the development of IL-6-mediated systemic inflammatory response syndrome (SIRS). A 58-year-old woman presented with dyspnea and flank pain accompanied by SIRS and acute cardiac, kidney, and liver injuries. A left paravertebral mass was incidentally observed on abdominal computed tomography (CT). Biochemical tests revealed increased 24-hour urinary metanephrine (2.12 mg/day), plasma norepinephrine (1,588 pg/mL), plasma normetanephrine (2.27 nmol/L), and IL-6 (16.5 pg/mL) levels. ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/CT showed increased uptake of FDG in the left paravertebral mass without metastases. The patient was finally diagnosed with functional paraganglioma crisis. The precipitating factor was unclear, but phendimetrazine tartrate, a norepinephrine-dopamine release drug that the patient regularly took, might have stimulated the paraganglioma. The patient's body temperature and blood pressure were well controlled after alpha-blocker administration, and the retroperitoneal mass was surgically resected successfully. After surgery, the patient's inflammatory, cardiac, renal, and hepatic biomarkers and catecholamine levels improved. In conclusion, our report emphasizes the importance of IL-6-producing PPGLs in the differential diagnosis of SIRS.

• The Korean Journal of Pharmacology
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• v.21 no.1
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• pp.49-61
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• 1985

In view of the facts that dopamine (DA) when given directly into a lateral ventricle (i.c.v.) of the rabbit brain induces antidiuresis and that haloperidol, a non-specific antagonist of DA receptors, produces anti-diuresis in smaller doses and diuresis and natriuresis in larger doses, the present study was undertaken to delineate the roles of various DA receptors involved in the center-mediated regulation of renal function. Bromocriptine (BRC), a relatively specific agonist of D-2 receptors and at the same time a D-,1 antagonist, elicited natriuresis and diuresis when given i.c.v. in doses ranging from 20 to 600 {\mu}g/kg$, roughly in dose-related fashion, while the renal perfusion and glomerular filtration progressively decreased with doses, indicating that the diuretic, natriuretic action resides in the tubules, not related to the hemodynamic effects. These diuresis and natriuresis were most marked with 200 ${\mu}g/kg$, with the fractional sodium excretion reaching about 10%. With 600 ${\mu}g/kg$, however, the diuretic, natriuretic action was preceded by a transient oliguria resulting from severe reduction of renal perfusion, concomitant with marked but transient hypertension. When given intravenously, however, BRC produced antidiuresis and antinatriuresis along with decreases in renal hemodynamics associated with systemic hypotension, thus indicating that the renal effects produced by i.c.v. BRC is not caused by a direct renal effects of the agent which might have reached the systemic circulation. In experiments in which DA was given i.c.v. prior to BRC, 150 ${\mu}g/kg$ DA did not affect the effects of BRC (200 ${\mu}g/kg$), while 500 ${\mu}g/kg$ DA abolished the BRC effect. In rabbits treated with reserpine, 1 mg/kg i.v.,24 h prior to the experiment, i.c.v. BRC could unfold its renal effects not only undiminished but rather exaggerated and more promptly. In preparations in which one kidney is deprived of nervous connection, the denervated kidney responded with marked diuresis and natriuresis, whereas the innervated, control kidney exhibited antidiuresis. These observations suggest that i.c.v. BRC influences the renal function through release of some humoral natriuretic factor as well as by increasing sympathetic tone, and that various DA receptors might be involved with differential roles in the center-mediated regulation of the renal function.