• The Korean Journal of Pain
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• v.12 no.2
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• pp.177-182
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• 1999

Background: Clonidine, an ${\alpha}_2$ adrenergic agonist blocks nerve conduction. However, in our previous experiment we found that adrenaline neither blocks nerve conduction by itself nor augment nerve conduction blockade by lidocaine near clinical concentrations. Possible explanations are: 1) there may be antagonism between some of adrenergic receptors, 2) clonidine may block nerve conduction via non-adrenergic mechanism. The purpose of this study is to obtain dose-response curves of several different forms of adrenergic receptor agonist to see the relative potencies of each adrenergic receptors to block nerve conduction. Methods: Recordings of compound action potentials of A-fiber components (A-CAPs) were obtained from isolated sciatic nerves of adult male Sprague-Dawley rats. Nerve sheath of the sciatic nerve was removed and desheathed nerve bundle was mounted on a recording chamber. Single pulse stimuli (0.5 msec, supramaximal stimuli) were repeatedly applied (2Hz) to one end of the nerve and recordings of A-CAPs were made on the other end of the nerve. Dose-response curves of epinephrine, phenylephrine, isoproterenol, clonidine were obtained. Results: $ED_{50}$ of each adrenergic agonist was: $4.51\times10^{-2}$ M for epinephrine; phenylephrine, $7.74\times10^{-2}$ M; isoproterenol, $9.61\times10^{-2}$ M; clonidine, $1.57\times10^{-3}$ M. Conclusion: This study showed that only clonidine, ${\alpha}_2$ adrenergic agonist, showed some nerve blocking action while other adrenergic agonists showed similar poor degree of nerve blockade. This data suggest that non-effectiveness of epinephrine in blocking nerve conduction is not from the antagonism between adrenergic receptors.

• The Korean Journal of Pain
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• v.9 no.2
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• pp.318-325
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• 1996

Background: Sympathectomy relieves pain in sympathectically maintained pain, and subcutaneous injection of norepinephrine(NE) can rekindle mechanical allodynia. However, the mechanism of rekindling is not clear. The purpose of this study is to investigate which subtype of $\alpha$-adrenoceptor is involved in NE-induced rekindling of mechanical allodynia in sympathectomized neuropathic rats. Methods: Neuropathic injury was produced by tightly ligating the left L5 and L6 spinal nerves of 36 male Sprague-Dawley rats and bilateral lumbar sympathectomy was done at two weeks postoperatively. Starting at 7 days after sympathectomy, rekindling of mechanical allodynia was induced by NE and clonidine injected into the left paw, which was reversed by pretreatment of phentolamine and idazoxan. Mechanical allocynia was quantified by measuring the frequency of foot lifts to two von Frey filaments applied to the paw. Results: All tested rats displayed well-developed signs of mechanical allodynia at the left paw that were abolished by a bilateral lumbar sympathectomy. Subcutaneous (s.c.) injection of NE (0.05 ${\mu}g$) into the affected paw of sympathectomized neuropathic rats rekindled previous mechanical allodynia. These effects could be mimicked by an ${\alpha}_2$-receptor agonist clonidine, but not by an ${\alpha}_1$-receptor agonist phenylephrine. The NE-induced rekindling of mechanical allodynia was significantly reduced by prior s.c. injection of a mixed $\alpha$-receptor antagonist phentolamine (20${\mu}g$) and ${\alpha}_2$-receptor antagonist idazoxan(20${\mu}g$), but not by a ${\alpha}_1$-receptor antagonist terazosin (20${\mu}g$). The pretreatment of idazoxan produced dose-related inhibition of NE-induced rekindling of mechanical allodynia. The rekindling induced by ${\alpha}_2$-receptor agonist clonidine (5${\mu}g$) was also reversed by prior s.c. injection of ${\alpha}_2$-receptor antagonist idazoxan (20${\mu}g$). Conclusion: Subcutaneous injection of NE into the paw of sympathectomized neuropathic rats rekindles mechanical allodynia, which is reversed by an ${\alpha}_2$-, but not by an ${\alpha}_1$-receptor antagonist. Therefore, rekindling of mechanical allodynia in sympathectomized neuropathic rats is mediated by ${\alpha}_2$-adrenoceptor.

• Biomolecules & Therapeutics
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• v.8 no.2
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• pp.132-139
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• 2000

This study was performed far investigation of influence on renal function of idazoxan, $\alpha_{2}$-adrenergic antagonist, using the dog. Idazoxan, when giver. into vein, produced the decrease of urine volume(vol) accompanied with the reduction of free water clearance($C_{H2O}$), amounts of sodium excreted in urine($E_{Na}$), with the increase of potassium excreted in urine($E_{K}$), and so ratios of potassium against sodium($K^{+}/Na^{+}$) were elevated, at this time, greatened reabsorption rate of sodium and diministered that of potassium in renal tubules were appeared. Idazoxan administered into a renal artery elicited the augmentation of vol, glomerular filtration rate(GFR), renal plasma flow(RPF) and no change of filtration fraction(FF) in only ipsilateral kidney, whereas $E_{Na},\;E_{K}\;and\;K^{+}/Na^{+}$ were increased and $C_{H2O}$ was decreased in both control and experimental kidney. Idazoxan given into carotid artery showed partial increased vol, remarkable expanded RPF and unchanged GFR, and so filtration fraction(FF) was markedly reduced. Above results suggest that anti- diuretic action of idazoxan given into vein is mediated by reduction of $C_{H2O}\;and\;E_{Na}$, diuretic action only in the ipsilateral kidney by idazoxan given into a renal artery is caused by hemodynamic improvement through expansion of vas afferens in glomeruli.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.495-507
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• 2017

The effect of clonidine administered intrathecally (i.t.) on the mortality and the blood glucose level induced by sepsis was examined in mice. To produce sepsis, the mixture of D-galactosamine (GaLN; 0.6 g/10 ml)/lipopolysaccharide (LPS; $27{\mu}g/27{\mu}l$) was treated intraperitoneally (i.p.). The i.t. pretreatment with clonidine ($5{\mu}g/5{\mu}l$) increased the blood glucose level and attenuated mortality induced by sepsis in a dose-dependent manner. The i.t. post-treatment with clonidine up to 3 h caused an elevation of the blood glucose level and protected sepsis-induced mortality, whereas clonidine post-treated at 6, 9, or 12 h did not affect. The pre-treatment with oral D-glucose for 30 min prior to i.t. post-treatment (6 h) with clonidine did not rescue sepsis-induced mortality. In addition, i.t. pretreatment with pertussis toxin (PTX) reduced clonidine-induced protection against mortality and clonidine-induced hyperglycemia, suggesting that protective effect against sepsis-induced mortality seems to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Moreover, pretreatment with clonidine attenuated the plasma tumor necrosis factor ${\alpha}$ ($TNF-{\alpha}$) induced by sepsis. Clonidine administered i.t. or i.p. increased $p-AMPK{\alpha}1$ and $p-AMPK{\alpha}2$, but decreased p-Tyk2 and p-mTOR levels in both control and sepsis groups, suggesting that the up-regulations of $p-AMPK{\alpha}1$ and $p-AMPK{\alpha}2$, or down-regulations of p-mTOR and p-Tyk2 may play critical roles for the protective effect of clonidine against sepsis-induced mortality.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.2
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• pp.119-123
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• 2012

In the present study, the antinociceptive profiles of $Agrimonia$ $pilosa$ $Ledeb$ extract were examined in ICR mice. $Agrimonia$ $pilosa$ $Ledeb$ extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, $Agrimonia$ $pilosa$ $Ledeb$ extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 ${\mu}g$) was diminished by $Agrimonia$ $pilosa$ $Ledeb$ extract. Intraperitoneal (i.p.) pretreatment with yohimbine (${\alpha}_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by $Agrimonia$ $pilosa$ $Ledeb$ extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by $Agrimonia$ $pilosa$ $Ledeb$ extract in the writhing test. Our results suggest that $Agrimonia$ $pilosa$ $Ledeb$ extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of $Agrimonia$ $pilosa$ $Ledeb$ extract may be mediated by ${\alpha}_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• The Korean Journal of Physiology
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• v.7 no.2
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• pp.59-66
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• 1973

It has been reported that vasopressin disperse the melanophore granule of frog skin. The author used hypophysectomized and adrenergic receptor blockaded animals in order to define the mechanism of vasopressin on the melanopore pigment of frog skin. The Rana niglomaculata which could be found in the Seoul area were used on this experiment. The amount of the following drugs were injected into the lymphatic sac of the frog; vaospressin $(0.05\;{\mu}g/g\;B.W.)$, dibenzylin $(0.05\;{\mu}g/g\;B.W.)$, and propranolol $(0.01\;{\mu}g/g\;B.W.)$. The following results were observed; 1. Vasopressin dispersed the melanin granules of melanocyte of frog skin. 2. The melanin granule dispersion activity of vasopressin was observed on the hypophysectomized frog. 3. The melanin granule dispersion was observed on the adrenergic receptor blockaded frog with dibenzylin or propranolol respectively, especially the later one was found to be more obvious. 4. The melanin granule dispersion was observed on the frog which was injected with vasopressin after alpha-receptor or beta-receptor blockade and the later one was found to be more obvious. 5. The melanin granule dispersion was more effective with the blockade of beta-receptor after the treatment with vasopressin on hypophysectomized frog.

• Korean Journal of Medicinal Crop Science
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• v.18 no.4
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• pp.238-243
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• 2010

In the present study, the antinociceptive profiles of Viola tricolor L. (V. tricolor L.) extract were examined in ICR mice. V. tricolor L. extract administered orally (200mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, V. tricolor L. extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 ${\mu}g$) was diminished by V. tricolor L. extract. Intraperitoneal (i.p.) pretreatment with yohimbine (${\alpha}_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by V. tricolor L. extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by V. tricolor L. extract in the writhing test. Our results suggest that V. tricolor L. extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of V. tricolor L. extract may be mediated by ${\alpha}_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.5
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• pp.285-289
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• 2010

In the present study, the antinociceptive profiles of $Campanula$ $punctata$ extract were examined in ICR mice. The $Campanula$ $punctata$ contain a large dose of saponin. $Campanula$ $punctata$ extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, $Campanula$ $punctata$ extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P ($0.7{\mu}g$) was diminished by $Campanula$ $punctata$ extract. Intraperitoneal (i.p.) pretreatment with yohimbine (${\alpha}_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by $Campanula$ $punctata$ extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by $Campanula$ $punctata$ extract in the writhing test. Our results suggest that $Campanula$ $punctata$ extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of $Campanula$ $punctata$ extract may be mediated by ${\alpha}_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• Journal of Acupuncture Research
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• v.20 no.2
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• pp.85-97
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• 2003

Introduction : In this study, the analgesic effect and its mechanism of bee venom aqua-acupuncture on complete Freund's adjuvant-induced arthritis in rats was investigated. It has been reported from a neurochemical standpoint that bee venom exerts antinociceptive effects on inflammation and that the opioid system and adrenergic system play important roles in acupuncture analgesia. however, it is not known whether central opioid and ${\alpha}2$-adrenergic components of the intrinsic descending analgesic system are activated after bee venom aqua-acupuncture. Methods : Bee venom(1mg/kg) was subcutaneously aqua-acupunctured into Joksamni($ST_{36}$) of rats with complete Freund's adjuvant(CFA)- induced arthritis and was checked of increase in TFL. Opioid and ${\alpha}_2$-adrenergic neurotransmitter system were examined by naloxone as an opioid receptor antagonist, and yohimbine as ${\alpha}_2$-adrenoceptor antagonist prior to bee venom aqua-acupuncture. Results : The following results have been obtained. 1. The tail flick latency in the rat model with adjuvant-induced arthritis was significantly decreased in 2 weeks. 2. The tail flick latency in the rat model with adjuvant-induced arthritis was increased in bee venom aqua-acupuncture group compared to the normal saline aqua-acupuncture group. 3. Analgesic effect of bee venom was antagonized by yohimbine not by naloxone pretreatment in the rat model adjuvant-induced arthritis. Conclusions : Bee venom aqua-acupuncture has an analgesic effect on the rat model of adjuvant-induced of adjuvant-induced arthritis and has antinociception mediated by ${\alpha}_2$-adrenergic system.

• Korean Journal of Veterinary Service
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• v.19 no.2
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• pp.154-162
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• 1996

The effcets of adenosine 5'-triphosphate(ATP) were investigated on the uterine smooth muscle motility in the pig. The results were summarized as follows: 1. The effects of the porcine uterine smooth muscle and the contractile responses increased between the concentration of ATP $10^{-5}$ and $10^{-3}$ M with a dose-dependent manner. 2. The contractile response induced by ATP($10^{-4}$ M) was not blocked by pretreatment with cholinergic receptor blocker, atropine ($10^{-6}$ M) 3. The contractile response induced by ATP ($10^{-4}$ M) was not blocked by pretreatment with $\alpha$ -adrenergic receptor blocker, phentolamine(10$^{-6}$ M) and ${\beta}$-adrenergic blocker, propranolol ($10^{-6}$ M). 4. The contractile response induced by ATP($10^{-4}$ M) was not appeared in 4Ca^{++}$ -free medium. As the concentration of $Ca^{++}$ in $Ca^{++}$ -free medium was increased, the contractile response induced by ATP ($10^{-4}$ M) was enhenced but was completely inhibited by pretreatment with $Ca^{++}$ -channel blocker, papaverine($10^{-6}$ M) or verapamil($10^{-6}$ M). From these results, it was conclued that the effects of ATP were the contraction mediated by purinergic receptor in uterine smooth muscle of pig.