• Molecules and Cells
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• v.21 no.3
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• pp.337-342
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• 2006

Interstitial cells of Cajal (ICCs) are pacemaker cells that activate the periodic spontaneous depolarization (pacemaker potentials) responsible for the production of slow waves in gastrointestinal smooth muscle. The effects of vasoactive intestinal polypeptide (VIP) on the pacemaker potentials in cultured ICCs from murine small intestine were investigated by whole-cell patch-clamp techniques. Addition of VIP (50 nM-$1{\mu}M$) decreased the amplitude of pacemaker potentials and depolarized resting membrane potentials. To examine the type of receptors involved in ICC, we examined the effects of the $VIP_1$ agonist and found that it had no effect on pacemaker potentials. Pretreatment with $VIP_1$ antagonist ($1{\mu}M$) for 10 min also did not block the VIP (50 nM)-induced effects. On the other hand exposure to 1H-(1,2,4)oxadiazolo(4,3-A)quinoxalin-1-one (ODQ, $100{\mu}M$), an inhibitor of guanylate cyclase, prevented VIP inhibition of pacemaker potentials. Similarly KT-5823 ($1{\mu}M$) or RP-8-CPT-cGMPS ($10{\mu}M$), inhibitors of protein kinase G (PKG) blocked the effect of VIP (50 nM) on pacemaker potentials as did N-nitro-L-arginine (L-NA, $100{\mu}M$), a non-selective nitric oxide synthase (NOS) inhibitor. These results imply that the inhibition of pacemaker activity by VIP depends on the NO-cGMP-PKG pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.4
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• pp.341-346
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• 2014

Lubiprostone is a chloride ($Cl^-$) channel activator derived from prostaglandin $E_1$ and used for managing constipation. In addition, lubiprostone affects the activity of gastrointestinal smooth muscles. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow-wave activity in smooth muscles. We studied the effects of lubiprostone on the pacemaker potentials of colonic ICCs. We used the whole-cell patch-clamp technique to determine the pacemaker activity in cultured colonic ICCs obtained from mice. Lubiprostone hyperpolarized the membrane and inhibited the generation of pacemaker potentials. Prostanoid $EP_1$, $EP_2$, $EP_3$, and $EP_4$ antagonists (SC-19220, PF-04418948, 6-methoxypyridine-2-boronc acid N-phenyldiethanolamine ester, and GW627368, respectively) did not block the response to lubiprostone. L-NG-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) did not block the response to lubiprostone. In addition, tetraethylammonium (TEA, a voltage-dependent potassium [$K^+$] channel blocker) and apamin (a calcium [$Ca^{2+}$]-dependent $K^+$ channel blocker) did not block the response to lubiprostone. However, glibenclamide (an ATP-sensitive $K^+$ channel blocker) blocked the response to lubiprostone. Similar to lubiprostone, pinacidil (an opener of ATP-sensitive $K^+$ channel) hyperpolarized the membrane and inhibited the generation of pacemaker potentials, and these effects were inhibited by glibenclamide. These results suggest that lubiprostone can modulate the pacemaker potentials of colonic ICCs via activation of ATP-sensitive $K^+$ channel through a prostanoid EP receptor-independent mechanism.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.874-883
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• 2007

The aqueous extract of Chungsimyeonja-eum has been used to treat palpitation, anemia, chronic fatigue, hypertension, and stroke. It also possesses various pharmacological effects including hypotensive, blood circulating, sedative, anti-inflammatory, diuretic, and anti-stress activities. In the present results, the latency time of plantar test was decreased in the immobilization stress and incusion pain-induction group. However the paw withdrawal latency values were increased in the immobilization stress and incision pain-induction groups after treatment with the aqueous extract of Chungsimyeonja-eum. The c-Fos expression in the paraventricular nucleus (PVN), and 5-hydroxytryptamine (5-HT) and tryptophan hydroxylase (TPH) in the dorsal raphe were enhanced in the immobilization stress and incision pain-induction groups. However, the treatment with the aqueous extract of Chungsimyeonja-eum suppressed the immobilization stress and incision pain-induced increase of c-Fos, 5-HT, and TPH expressions. Here in this study, we have demonstrated the protective effects of Chungsimyeonja-eum on immobilization and incision pain-induced stress. The present study revealed that Chungsimyeonja-eum treatment diminishes immobilization and pain stress.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.349-355
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• 2015

We examined the effects of peripherally or centrally administered botulinum neurotoxin type A (BoNT-A) on orofacial inflammatory pain to evaluate the antinociceptive effect of BoNT-A and its underlying mechanisms. The experiments were carried out on male Sprague-Dawley rats. Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase. Both subcutaneous (1 or 3 U/kg) and intracisternal (0.3 or 1 U/kg) injection of BoNT-A increased the latency of head withdrawal response in the complete Freund's adjuvant (CFA)-treated rats. Intracisternal administration of N-methyl-D-aspartate (NMDA) evoked nociceptive behavior via the activation of trigeminal neurons, which was attenuated by the subcutaneous or intracisternal injection of BoNT-A. Intracisternal injection of NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Subcutaneous (3 U/kg) or intracisternal (1 U/kg) administration of BoNT-A significantly reduced the number of c-Fos immunoreactive neurons in the NMDA-treated rats. These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons. Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.1
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• pp.15-20
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• 2007

To investigate whether hydrogen peroxide($H_2O_2$) affects intestinal motility, pacemaker currents and membrane potential were recorded in cultured interstitial cells of Cajal(ICC) from murine small intestine by using a whole-cell patch clamp. In whole cell patch technique at $30^{\circ}C$, ICC generated spontaneous pacemaker potential under current clamp mode(I=0) and inward currents(pacemaker currents) under voltage clamp mode at a holding potential of -70 mV. When ICC were treated with $H_2O_2$ in ICC, $H_2O_2$ hyperpolarized the membrane potential under currents clamp mode and decreased both the frequency and amplitude of pacemaker currents and increased the resting currents in outward direction under voltage clamp mode. Also, $H_2O_2$ inhibited the pacemaker currents in a dose-dependent manner. Because the properties of $H_2O_2$ action on pacemaker currents were same as the effects of pinacidil(ATP-sensitive $K^+$ channels opener), we tested the effects of glibenclamide(ATP-sensitive $K^+$ channels blocker) on $H_2O_2$ action in ICC, and found that the effects of $H_2O_2$ on pacemaker currents were blocked by co- or pre- treatment of glibenclamide. These results suggest that $H_2O_2$ inhibits pacemaker currents of ICC by activating ATP-sensitive $K^+$ channels.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.5
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• pp.253-258
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• 2008

Somatostatin (SOM) is a widely distributed peptide in the central nervous system and exerts a variety of hormonal and neural actions. Although SOM is assumed to play an important role in spinal nociceptive processing, its exact function remains unclear. In fact, earlier pharmacological studies have provided results that support either a facilitatory or inhibitory role for SOM in nociception. In the current study, the effects of SOM were investigated using anesthetized cats. Specifically, the responses of rostrally projecting spinal dorsal horn neurons (RPSDH neurons) to different kinds of noxious stimuli (i.e., heat, mechanical and cold stimuli) and to the $A{\delta}$ -and C-fiber activation of the sciatic nerve were studied. Iontophoretically applied SOM suppressed the responses of RPSDH neurons to noxious heat and mechanical stimuli as well as to C-fiber activation. Conversely, it enhanced these responses to noxious cold stimulus and $A{\delta}$-fiber activation. In addition, SOM suppressed glutamate-evoked activities of RPSDH neurons. The effects of SOM were blocked by the SOM receptor antagonist cyclo-SOM. These findings suggest that SOM has a dual effect on the activities of RPSDH neurons; that is, facilitation and inhibition, depending on the modality of pain signaled through them and its action site.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.748-754
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• 2007

Electroacupuncture is the combined treatment of mechanical and electric stimuli on the needle head, on which electricity runs after acupuncturing at the acupuncture points. It is reported that its treatment effect depends on the parameter of stimulus, which is wave of stimulus, frequency, voltage, and duration of electric current. To get the effective treatment, stimulus intensity over threshold is needed. We planned to experiment whether acupuncture effect is affected by sex, age, and weight. After we conducted electric stimulus at Zusanli(ST 36) which is known to increase small intestinal motility in normal rats, we observed the effects and got the following results. Though the increased effects of small intestinal motility of electro-acupuncture at Zusanli(ST 36) did not show the difference of sex, this effect was observed to have a tendency to decrease according to weight increase without distinction of sex. But the effect of electro-acupuncture shown in 4, 5, 7 weeks old without distinction of sex was observed to have a tendency to decrease with the growing of weeks-old in the male rat group. And the significant change without specific tendency was observed in the 4, 5 weeks old female rat group. This result suggested that sex, weight, and age should be considered to get the efficient electro-acupuncture. The more experimental study should be advanced to investigate the correlation between the factors that can affect the acupuncture treatment, and, afterward, the interconnection into the clinical use.

• The Korean Journal of Pain
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• v.37 no.3
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• pp.211-217
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• 2024

Background: Tolerance to the analgesic effects of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is a major concern for relieving pain. Thus, it is highly valuable to find new pharmacological strategies for prolonged therapeutic procedures. Biguanide-type drugs such as metformin (MET) are effective for neuroprotection and can be beneficial for addressing opioid tolerance in the treatment of chronic pain. It has been proposed that analgesic tolerance to NSAIDs is mediated by the endogenous opioid system. According to the cross-tolerance between NSAIDs, especially sodium salicylate (SS), and opiates, especially morphine, the objective of this study was to investigate whether MET administration can reduce tolerance to the anti-nociceptive effects of SS. Methods: Fifty-six male Wistar rats were used in this research (weight 200-250 g). For induction of tolerance, SS (300 mg/kg) was injected intraperitoneally for 7 days. During the examination period, animals received MET at doses of 50, 75, or 100 mg/kg for 7 days to evaluate the development of tolerance to the analgesic effect of SS. The hot plate test was used to evaluate the drugs' anti-nociceptive properties. Results: Salicylate injection significantly increased hot plate latency as compared to the control group, but the total analgesic effect of co-treatment with SS + Met50 was stronger than the SS group. Furthermore, the effect of this combination undergoes less analgesic tolerance over time. Conclusions: It can be concluded that MET can reduce the analgesic tolerance that is induced by repeated intraperitoneal injections of SS in Wister rats.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.1
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• pp.220-224
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• 2003

To test the protective effect of Sophorae Radix (SR) on the damage of cardiac endothelial cells by xanthine oxidase (XO)/hypoxanthine (HX)-induced oxygen tree radical, Neutral Red (NR), lactate dyhydrogenase (LDH), and c-fos immunopositive cells assay were used in the presence of SR extract. The results of these experiments were obtained as follows ; Cardiac endothelial cells treated with XO/HX showed the cytotoxicity such as a decrease in viability, and increases in LDH activity and c-fos immunopositive cells. Cardiac endothelial cells pretreated with SR extract protected the increase of LDH activity. Alos, cardiac endothelial cells pretreated with SR extract inhibited the increase of c-fos immunopositive cells. These results show that XO/HX induces toxic effects in cultured cardiac endothelial cells derived from neonatal rat, and suggest that SR extract is very effective in the prevention of XO/HX-induced toxicity.

• Journal of The Korean Society of Grassland and Forage Science
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• v.38 no.3
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• pp.180-189
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• 2018

The present study was conducted to evaluate the effects of high levels of nutrients on the growth performance, blood metabolites and carcass characteristics of Hanwoo cattle. Eighteen Hanwoo steers were fed two types of diets: 1) Nine animals were fed the conventional diet including typical levels of crude protein (CP) and total digestive nutrients (TDN), and 2) Nine animals were fed the treatment diet including high levels of CP and TDN. The average body weight (BW) and dry matter intake (DMI) were greater (P < 0.05) in the treatment group than in the conventional group at early and late fattening stages. Also, in the treatment group, the average daily gain (ADG) was greater (P < 0.05) at the late fattening stage. The serum total lipid and cholesterol levels were higher (P < 0.05) in the late fattening stage of treatment group. The carcass weight, total fat weight, longissimus muscle area and the grade of meat quality were also greater (P < 0.05) in the treatment group than the conventional diet group. This study demonstrates that high levels of CP and TDN exhibit a positive effect on the growth performance and carcass characteristics, indicating that high levels of CP and TDN can be used as a cost-effective feeding program for Hanwoo cattle by shortening the feeding period.