Calcium Ions are Involved in Modulation of Melittin-induced Nociception in Rat: I. Effect of Voltage-gated Calcium Channel Antagonist

신홍기,이경희 대한약리학회 2006 The Korean Journal of Physiology & Pharmacology Vol.10 No.5

Melittin-induced nociceptive responses are mediated by selective activation of capsaicin-sensitive primary afferent fibers and are modulated by excitatory amino acid receptor, cyclooxygenase, protein kinase C and serotonin receptor. The present study was undertaken to investigate the peripheral and spinal actions of voltage-gated calcium channel antagonists on melittin-induced nociceptive responses. Changes in mechanical threshold and number of flinchings were measured after intraplantar (i.pl.) injection of melittin (30μg/paw) into mid-plantar area of hindpaw. L-type calcium channel antagonists, verapamil [intrathecal (i.t.), 6 or 12μg; i.pl.,100 & 200μg; i.p., 10 or 30 mg], N-type calcium channel blocker, ω-conotoxin GVIA (i.t., 0.1 or 0.5μg; i.pl., 5μg) and P-type calcium channel antagonist, ω- agatoxin IVA (i.t., 0.5μg; i.pl., 5μg) were administered 20 min before or 60 min after i.pl. injection of melittin. Intraplantar pre-treatment and i.t. pre- or post-treatment of verapamil and ω-conotoxin GVIA dose-dependently attenuated the reduction of mechanical threshold, and melittin-induced flinchings were inhibited by i.pl. or i.t. pre-treatment of both antagonists. P-type calcium channel blocker, ω- agatoxin IVA, had significant inhibitory action on flinching behaviors, but had a limited effect on melittin-induced decrease in mechanical threshold. These experimental findings suggest that verapamil and ω-conotoxin GVIA can inhibit the development and maintenance of melittin-induced nociceptive responses.

아편양 물질의 내약성

신홍기 한양대학교 의과대학 1998 한양의대 학술지 Vol.18 No.1

Morphine and related opioid substances are probably the most widely used analgesics but chronic exposure to them leads to the development of tolerance characterized by their reduced ability to induce analgesic action and dependence. Extensive studies have been made to elucidate the mecahnisms by which toleracne or dependence is produced but their underlying mechanisms are still not clear. Morphine tolerance is characterized by the increases in the sensitivity of NMDA (N-methyl-D-aspartate) receptor, intracellular Ca^2+ level, membrane bound PKC (protein kinase C) and production of NO (nitric oxide), which are also known to be implicated in the development of hyperalgesia. Therefore, the development of tolerance or hyperalgesia is antagonized by the administration of NMDA receptor antagonist, Ca^2+ channel blocker, PKC inhibitor and NO synthase inhibitor. However, cholecystokinin and cAMP aggravate the development of morphine tolerance. These recent findings suggest that the common intracellular mechanisms are implicated in both hyperalgesia and morphine tolerance.

Calcium Ions Are Involved in Modulation of the Melittin-induced Nociception in Rat: II. Effect of Calcium Chelator

신홍기,이희경,조철현 대한약리학회 2006 The Korean Journal of Physiology & Pharmacology Vol.10 No.6

Melittin, a major component of bee venom, produces a sustained decrease in mechanical threshold, and an increase in spontaneous flinchings and paw thickness, which are characteristics similar to those induced by whole bee venom. Melittin-induced nociception has been known to be modulated by the changes in the activity of excitatory amino acid receptors, voltage-dependent calcium channels, cyclooxygenase and serotonin receptors. The present study was undertaken to investigate the role of calcium chelators (TMB-8 & Quin 2) in melittin-induced nociceptive responses. Changes of mechanical threshold and spontaneous flinching behaviors were measured at a given time point following intraplantar injection of melittin (30μg/paw). Intrathecal or intraplantar pre-administration and intrathecal post- treatment of TMB-8 and Quin 2 significantly prevented the melittin-induced reduction of mechanical threshold, and intraplantar or intrathecal pre-treatment of TMB-8 and Quin 2 suppressed melittin- induced flinching behaviors. These results indicate that calcium ion in the spinal dorsal horn neurons and peripheral nerves plays an important role in the production and maintenance of mechanical allodynia and spontaneous pain by melittin.

Low-Temperature Dielectric Relaxation in Ferroelectric Pyridinium Tetrafluoroborate

신홍기 한국물리학회 2015 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.67 No.5

The dielectric behavior of polycrystalline pyridinium tetrafluoroborate, C5NH6BF4, has been investigated in detail at temperatures in the range of 120 K T 280 K and frequencies in the range of 10 Hz 105 Hz. The marked dielectric dispersion observed at temperatures below 205 K was analyzed by using the sum of two different relaxation processes. The temperature dependence of the relaxation time for the main one with dominant strength revealed an excellent fit to the Arrhenius equation with an activation energy E = 2702 ± 6 K and a pre-exponential factor 0 = 2.2 × 10−11 s. The coupled reorienting motion of the pyridinium cation and the BF4 anion is suggested to account for the main process. The relaxation time for the other weak process also obeys the Arrhenius law with E = 815±14 K and 0 = 7.9×10−5 s. The origin of the weak process is ascribed to the ferroelectric domain-wall motion.

Multiple 5-Hydroxytryptamine (5-HT) Receptors Are Involved in the Melittin-induced Nociceptive Responses in Rat I. Role of Peripheral 5-HT Receptor

신홍기,이서은 대한약리학회 2007 The Korean Journal of Physiology & Pharmacology Vol.11 No.5

Melittin-induced tonic pain model is characterized by local inflammation, edema, spontaneous flinchings, and sustained mechanical hypersensitivity. These nociceptive responses are mediated through selective activation of capsaicin-sensitive primary afferent fibers by melittin. The present study was undertaken to elucidate the role of peripheral 5-hydroxytryptamine (5-HT) receptors in the melittin-induced nociceptive responses. Changes in mechanical threshold, flinching behaviors and paw thickness were measured in rat intraplantarly injected with melittin (40μg/paw) alone or treated together with melittin and 5-HT receptor antagonists. WAY-100635 (100μg & 200μg/paw), isamoltane hemifumarate (100μg & 200μg/paw), methysergide maleate (60μg, 120μg & 200μg/paw) and ICS-205,930 (100μg & 200μg/paw) were intraplantarly injected 20 min before melittin injection. All 5-HT receptor antagonists tested in this experiment significantly attenuated the ability of melittin to reduce mechanical threshold and to induce flinching behaviors. 5-HT receptor antagonists, except ICS-205,930, had mild inhibitory effect on melittin-induced edema. These experimental findings suggest that multiple peripheral 5-HT receptors are involved in the melittin-induced nociceptive responses.

통증의 생리

신홍기 한양대학교 의과대학 2003 한양의대 학술지 Vol.23 No.1

상엽(桑葉)(Morus alba Linne)의 혈압강하작용(血壓降下作用)

신홍기,김기순,이경로,Shin, Hong-Kee,Kim, Kee-Soon,Lee, Kyung-Ro 대한생리학회 1979 대한생리학회지 Vol.13 No.1

The present study was undertaken to investigate effect of water extracts of the mulberry leaves (MWE) on arterial blood pressure and respiration in cats. And also studied were depressor responses to intravenously administered MWE in the animals pretreated separately with atropine(2.5 mg/kg), propranolol(2 mg/kg), dibenamine (15 mg/kg), and hexamethonium (1.5 mg/kg) in order to find out the mechanism of depressor activity of MWE. The results obtained were as follows; 1) Following intravenous administration of 0.25 ml/kg and 0.5 ml/kg of MWE into the cat the maximum depressor responses observed were $60.2{\pm}2.3\;mmHg$ and $72.3{\pm}1.7\;mmHg$ respectively. 2) Since depressor responses to intravenously administered MWE were partially inhibited by hexamethonium and markedly by atropine, it is strongly suggested that depressor activity of MWE mainly results from its vagal effects. 3) After administration of MWE respiratory rate was invariably increased following a short period of apnea.

전침자극이 흰쥐척수후각세포의 유해자극반응에 미치는 효과의 특성

신홍기,박동석,이서은,김진혁,Shin, Hong-kee,Park, Dong-suk,Lee, Seo-eun,Kim, Jin-hyuk 대한침구의학회 2002 대한침구의학회지 Vol.19 No.4

This experiment was designed to investigate the effects of electroacupuncture (EA) on chronic pains and factors that affected EA effects. The responses of wide dynamic range (WDR) cells to electrical stimulation of $A{\delta}$ & C afferent fibers were used as an index of pain in rats with chronic pains induced by intraplantar injection of complete Freund's adjuvant or peripheral nerve injury. In rats with chronic pains, low (2Hz) and high (100Hz) frequency EA stimulation applied to zusanli caused the inhibition of WDR cell responses in about 60% of rats and the inhibitory actions were dependent on the stimulus strength. EA stimulation also induced an excitation of WDR cell responses in 23.9% of rats and no effect in 15.8% of rats. However, it seemed that in normal rats compared to the rat with chronic pains, the incidence of which EA stimulation caused the excitation or no effect was high. Reversible spinalization almost completely blocked EA-induced inhibitory or excitatory effects. EA stimulation more frequently induced the excitation of WDR cell responses in lightly anesthetized (0.6%) rats and the enhanced responses of WDR cells were inhibited by EA stimulation in the rat anesthetized with 1.5% enflurane. These experimental findings suggest that in rats with chronic pain, EA stimulation inhibited WDR cell responses to slow $A{\delta}$ and C fiber stimulation and EA-induced inhibitory action was under the control of descending inhibitory system and degree of anesthesia.

밤 抽出液에 의한 血壓下作用

辛弘基 건국대학교 1978 論文集 Vol.8 No.1

The present study was undertaken to investigate effect of ethanol extract of chestnut and the mechanism of ifs action on arterial blood pressure in the cat. The results obtained are as follows; ① Intravenously injected ethanol extract of chestnut markedly reduced mean arterial blood pressure in the cat. At doses of 30 mg/kg and 50 mg/kg of chestnut extract the changes in mean arterial blood pressure were 31.7 ± 1.3 mmHg and 45.1 ± 1.5 mmHg respectively. ② The magnitude of depressor responses to chestnut extract were proportional to closes of chestnut extract intravenousely injected into animals. ③ There were no changes in the depressor responses to chestnut extract either in bilaterally vagotomized animals or in propranolol (2mg/kg) or dibenamine (1.5mg/kg) treated animals, while the depressor responses were markedly inhibited in anti-histamine (2.5mg/kg) treated cats. Therefore, it is strongly suggested that most of depressor effect of chestnut extract was due to its histamine-like action and a part of depressor effect to its direct action on vascular smooth muscle. ④ No effect on respiration of chestnut extract was observed.

視床下部內로 投與된 Tetrodotoxin이 動脈壓에 미치는 影響

辛弘基 한양대학교 의과대학 1982 한양의대 학술지 Vol.2 No.2

The present study was undertaken to investigate the effect of tetrodotoxin (TTX) on excitability of the hypothalamus to electrical stimulation and to find out if the hypothalamus has any tonic activity on the cardiovascular system by observing changes in bollod pressure and heart rate after intrahypothalamic administration of TTX. The results obtained are as follows: 1. After intrahypothalamic administration of 0.005㎍/㎏ and 0.01㎍/㎏ tetrodotoxin, the pressor responses to electrical stimulation of the hypothalamus were gradually reduced and at dosage of 0.01㎍/㎏ TTX the responses were almost abolished 30 seconds to 3 minutes after TTX administration. 2. After 0.05㎍/㎏ TTX administration arterial blood pressure and heart retd decreased significantly at 20 minutes and 15 minutes after TTX administration respectively. 3. In the cases 0.01㎍/㎏ TTX was administered, significant decrements in blood pressure and heart rate were observed respectively at 15 minutes and 10 minutes after TTX administration. 4. Since there were no significant decreases in blood pressure and heart rate immediately after tetrodotoxin administration, it is strongly suggested that the hypothalamus has no tonic activity to the cardiovascular system.