• The Korean Journal of Pharmacology
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• v.26 no.2
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• pp.127-133
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• 1990

Dibutyryl-cyclic AMP (db-cAMP) and forskolin were used to investigate vasodilating mechanism of cAMP in rabbit aorta. Db-cAMP and forskolin inhibited the development of contractile tension induced by norepinephrine (NE) concentration-dependently. However, high $K{^+}-induced$ contractile tension was inhibited less effectively by db-cAMP and forskolin. Db-cAMP and forskolin inhibited $^{45}Ca^{2+}$ uptake increased by NE. Forskolin seemed to inhibit $^{45}Ca^{2+}$ uptake increased by high $K{^+}$, but this inhibition was not significant statistically. Db-cAMP inhibited $Ca^{2+}-transient$ contraction by NE in $Ca^{2+}-free$ solution. In conclusion, it seems that cAMP blocks $Ca^{2+}$ influx through receptor operated $Ca^{2+}$ channels (ROCs), but that the effect of cAMP on $Ca^{2+}$ influx through voltage gated $Ca^{2+}$ channels (VGCs) is not clear in this experiment. Furthermore, cAMP is likely to inhibit calcium release from the intracellular stores.

• Progress in Medical Physics
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• v.11 no.1
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• pp.29-38
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• 2000

The signal transduction pathway for most neurotransmitter induced inhibition of $Ca^{2+}$ channels in sympathetic neurons involves a G-protein mediated, membrane-delimited mechanism without the participation of any known protein kinase. However, activation of protein kinase C (PKC) has been proposed as one of the intracellular mechanisms mediating some neurotransmitter induced $Ca^{2+}$ channel inhibition. In the present study, we investigated the effects of phorbol-12, 13-dibutyrate (PDBu) on $Ca^{2+}$ channel currents of acutely dispersed neurons from adult rat superior cervical ganglion (SCG) neurons using whole cell variant of the patch clamp technique. PDBu (500 nM), the activator of PKC, increased $Ca^{2+}$ channel currents and retarded the deactivation of tail currents. The effects of PDBu were voltage dependent and the maximal increase in the current amplitudes was observed between -10 to 10 mV (n=4). PDBu attenuated $Ca^{2+}$ current inhibition induced by norepinephrine (NE), which modulates $Ca^{2+}$ channels via a pertussis toxin (PTX)-sensitive pathway. Inhibition of PDBu by staurosporine (1 $\mu$M) blocked the effects of PDBu on current amplitudes and NE-induced G-protein mediated inhibition of $Ca^{2+}$ currents. Further experiment should be done to know if G-protein or $Ca^{2+}$ channel itself is the target of PKC phosphorvlation.phosphorvlation.

• The Journal of Internal Korean Medicine
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• v.16 no.1
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• pp.104-129
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• 1995

Sabaeksan and Sabaeksangagaryureuk, a traditional prescription, has been used in Korea for many centuries as a treatment for chronic respiratory disease. The purpose of the present study was to determine the effect of Sabaeksan and Sabaeksangagaryureuk on acetylcholine-induced tracheal smooth muscle contraction in guinea pigs and norepinephrine-induced vascular smooth muscle contraction in pigs. Guinea pig (500g, female) were killed by CO2 exposure and a segment (8-10mm) of the thoracic trachea from each guinea pig and renal artery from each pig were cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 0.5g loading tension. The dose of acetylcholine (Ach) and norepinephrine (NE) which evoked 50% of maximal response ($ED_{50}$) was obtained from cumulative dose response curves for acetylcholine (10-7-10-4M) and norepinephrine (10-7-10-4M). Contractions of tracheal smooth muscle evoked by Ach ($ED_{50}$) were inhibited significantly by Sabaeksan and Sabaeksangagaryureuk. Propranolol (10-7M) slightly but significantly attenuated the inhibitory effects of Sabaeksan and Sabaeksangagaryureuk. Indomethacin and methylene blue (10-7M) did not significantly alter the inhibitory effect of Sabaeksan and Sabaeksanga-garyureuk. Contractions of vascular smooth muscle evoked by NE (NE50) were inhibited significantly by Sabaeksan and Sabaeksangagaryureuk. Propranolol (10-7M) slightly but significantly attenuated the inhibitory effects of Sabaeksan and Sabaeksangagaryureuk. Indomethacin and methylene blue (10-7M) did not significantly alter the inhibitory effect of Sabaeksan and Sabaeksangagaryureuk. These results indicate that Sabaeksan and Sabaeksangagaryureuk can relax acetylcholine-induced contraction of guinea pig tracheal smooth muscle, and norepinephrine-induced contraction of pig vascular smooth muscle that this inhibition involves, in part, the relation of adrenergic receptor.

• Journal of Physiology & Pathology in Korean Medicine
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• v.38 no.1
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• pp.32-37
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• 2024

The aim of this study was to investigate the role of Daesiho-tang (Da Chai Hu-Tang) water extract (DSTE) in regulating chronic stress-induced cancer progression, focusing on its activity in modulating tumor-associated macrophages (TAMs). Different stimuli can polarize TAMs into immune-stimulating M1 macrophages or immunosuppressive M2 macrophages. During cancer progression, M2 phenotype increases and supports tumor growth, angiogenesis and metastasis. Notably, chronic stress-induced catecholamines promote M2 macrophage polarization. In this study, we investigated whether DSTE regulates norepinephrine (NE)-induced M2 macrophage polarization in RAW 264.7 mouse macrophage cells. Even though NE itself did not increase the expression of M2 markers, the conditioned media of NE-treated 4T1 mouse breast cancer cells (NE CM) significantly up-regulated M2 markers in RAW 264.7 cells, suggesting that NE-regulated cancer cell secretome stimulated M2 polarization. However, such increase was abrogated by DSTE. NE CM also induced phosphorylation of signal transducer and activator of transcription 6 (STAT6) in RAW 264.7 cells, which was clearly reversed by pretreatment with DSTE, demonstrating that DSTE inhibited M2 polarization by inactivating STAT6. Finally, M2-polarized RAW264.7 cells by NE CM markedly increased the migration of 4T1 cells. However, such increase was completely reversed by co-treating RAW264.7 cells with NE CM and DSTE, indicating that DSTE attenuated cancer cell migration by blocking M2 polarization. Taken together, our results suggest a probable use of DSTE for cancer patients under chronic stress by regulating M2 macrophage polarization.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.1
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• pp.55-61
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• 2000

The present study was conducted to investigate the possible role of the sympathetic nervous system in two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension. 2K1C and DOCA- salt hypertension were made in Sprague-Dawley rats. Four weeks after induction of hypertension, systolic blood pressure measured in conscious state was significantly higher in 2K1C $(216{\pm}18\;mmHg)$ and DOCA-salt $(205{\pm}29\;mmHg)$ groups than that in control $(128{\pm}4\;mmHg).$ The third branches (＜300 ${\mu}m$ in outer diameter) of the mesenteric artery were isolated and cut into ring segments of $2{\sim}3$ mm in length. Each ring segment was mounted in tissue bath and connected to a force displacement transducer for measurement of isometric tension. The arterial rings were contracted by application of norepinephrine (NE) in a dose-dependent manner. The amplitude of the NE-induced contraction of the vessels was significantly larger in hypertension than in control. The NE-induced contraction was significantly enhanced by neuropeptide Y (NPY) in hypertension. Reciprocally, NPY-elicited vasocontraction was increased by NE in hypertension. These results suggest that the sympathetic nervous system contributes to the development of 2K1C and DOCA-salt hypertension.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.9-14
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• 2002

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 in vivo, 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 $0.17{\pm}0.01,$ 3,4-dihydroxyphenylacetic acid (DOPAC) $0.94{\pm}0.07,$ homovanillic acid (HVA) $0.57{\pm}0.05$ 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 $(50\;{\mu}M)$ 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.

• Herbal Formula Science
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• v.7 no.1
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• pp.167-181
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• 1999

Rhizoma Arisaematis, Lignum Akebiae, Rhizoma Zedoariae, Cortex Eucommiae, Folium Perillae, Radix Sophorae Subprostratae, Radixi, Radix Ledeboutriellae, Rhizoma Atractylodis, Herba Ephedrae, Radix Puerariae and Radi Aconitx Bupleuri have been used in Korea for many centuries as a treatment for various disease. The purpose of the present study is to determine the effect of several herbs on norepinephrine(NE) induced blood vessel contraction in rabbits and pigs. Rabbit(2 kg, male) were killed by $CO_2$ exposure and a segment (8-10mm) of each rabbit was cut into equal segments and mounted in a tissue bath. Contractile force was measured with force displacement transducers under 2-3 g loading tension. The dose of norepinephrine(NE) which evoked 50% of maximal response $(ED_{50})$ was obtained from cumulative dose response curves for NE $(10^{-6}{\sim}10^{-3}M)$. Contractions evoked by NE $(ED_{50})$ were inhibited significantly by Rhizoma Arisaematis, Lignum Akebiae, Rhizoma Zedoariae, Cortex Eucommiae, Folium Perillae, Radix Sophorae Subprostratae and Herba Ephedrae in abdominal aorta. Contractions evoked by NE $(ED_{50})$ were inhibited significantly be Lignum Akebiae, Rhizoma Zedoariae, Cortex Eucommiae, Herba Ephedrae, Radix Puerariae and Radix Bupleuri in femoral artery. Contractions evoked by NE $(ED_{50})$ were inhibited significantly by Radix Sophorae Subprostratae, Radix Aconiti and Herba Ephedrae in renal artery. These results indicate that each herb can relax NE induced contraction of rabbit and pig blood vessel selectively, and that this relaxation relates to Gui-Gyung(歸經).

• Korean Journal of Acupuncture
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• v.29 no.2
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• pp.300-314
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• 2012

Objectives : This study is to observe the changes in the expression of neurotransmitters, such as NO, nNOS, and NE, upon the needle insertion to the sea points, which is one of the five transport points. Methods : Needles were inserted into rats, on both left and right sides of all sea points, including the LU5, PC3, HT3, LI11, TE10, SI8, SP9, LR8, KI10, ST36, GB34, and BL40, which are the sea points of five transport points for 12 meridian vessels. After insertion, needles were retained for five minutes. After the retention, blood was drawn via cardiac puncture, and tissues of each point near meridian vessels were extracted to examine the changes in the expression of NO, nNOS and NE. Results : In terms of the effect in NO production, there was a significant decrease only in the LU5 point, whereas there was a significant increase in the TE10 point alone. In terms of the expression of nNOS within tissues, none of the experimental groups showed significant changes based on the results of immunohistochemistry and western blotting. Regarding the formation of norepinephrine within tissues, the HT3, SP9, and KI10 point showed a significant decrease, while the PC3 and LR8 point showed a significant increase. Production of plasma norepinephrine was significantly increased at the TE10, SP9, LR8, GB34, and BL40 point. Conclusions : The effect of needles applied at the sea points of five transport points of 12 meridian vessels on the functions of NO, nNOS, and NE could be observed, and it is considered that the effect of needle stimulation on nervous system disorders could be studied through additional researches based on this one.

• Korean Journal of Acupuncture
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• v.32 no.4
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• pp.160-168
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• 2015

Objectives : This study was intended to observe the changes in the expression of neurotransmitters, such as nNOS, NO and NE upon the needle insertion at varying depths at the connecting point. Methods : Needles were inserted into rats, on both left and right sides of the connecting point, including the LI6, SI7 and TE5 acupoints which are three yang meridians of the hand. After insertion, needles were retained for five minutes. Each acupuncture groups were treated acupuncture at each acupoint and at the depths of superficial, middle and deep layer. After the retention, blood was drawn via cardiac puncture, and tissues of each point near meridian vessels were extracted to examine the changes in the expression of nNOS, NO and NE. Results : In terms of the effect in nNO production, there was a significant increase only in the middle and deep layer at SI7 acupoint, but there was no significant change in the expression of NO. Regarding the formation of norepinephrine within tissues, the middle layer on LI6 acupoint, the middle layer and the deep layer on TE5 acupoint showed a significant increase, while production of plasma norepinephrine was significantly decreased at the middle layer and the deep layer on LI6 acupoint and the deep layer on SI7 acupoint. Conclusions : The effect of needles applied at the connecting point of three yang meridians on the activities of nNOS, and NE could be observed, and it can be induced that the effect of needle stimulation on disrupted nervous system can be examined through additional researches based on this one.

• The Korean Journal of Pharmacology
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• v.6 no.1
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• pp.27-35
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• 1970

1) In whole anesthetized rabbits and spinal rabbits, the potentiating effect of syrosingopine and reserpine on pressor action of norepinephrine (NE) was compared. 2) The doses of syrosingopine and reserpine were 8, 40, $200\;{\mu}g$ and 1 mg per kg of body weight. The pressor responses to NE(0.1, 0.5, 0.25, 1.2, 6.0, 30.0, $150.0\;{\mu}g/kg$) were examine at 4, 10 and 24 hours after administration of the drugs. 3) In whole rabbits, potentiation by syrosingopine of pressor effect of NE was observed after administration of above the dose of $40\;{\mu}g/kg$, potentiation by reserpine was above $8\;{\mu}g/kg$. The maximal potentiation was achieved 10 hours after administration of $200\;{\mu}g/kg$ of each agent. 4) In spinal rabbits, syrosingopine $(200\;{\mu}g/kg)$ produced slight potentiation of pressor effect of NE. The same dose of reserpine produced more pronounced potentiation. 5) In the whole rabbits carbachol inhibited the potentiation observed 4 hours after administration of $40\;{\mu}g/kg$ of reserpine and syrosingopine. 6) In spinal rabbits, the potentiation observed 10 hours after $200\;{\mu}g/kg$ of reserpine and syrosingopine was inhibited by administration of carbachol. 7) The onset of potentiation of the pressor effect of NE was within 15 min after administration of syrosingopine and reserpine (1 mg/kg, each). 8) The above data suggest that the development of NE supersensitivity by syrosingopine and reserpine in rabbits has more intimate relationship with the decrease of central catecholamine contents than with that of peripheral ones. The depression of central sympathetic tone produced by these agents seems to play an important role in development of supersensitivity.