• Title/Summary/Keyword: alpha-2 agonist

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Norepinephrine-Induced Rekindling of Mechanical Allodynia in Sympathectomized Neuropathic Rat (교감신경절제 받은 신경병증성 통증 쥐 모델에서 Norepinephrine에 의해 유도된 기계적 이질통의 Rekindling의 기전)

  • Moon, Dong-Eon
    • 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.

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Control of Parturition Time on Pig II. Effect of Sympathetic Nerve and Adrenergic Agonist on Uterine Smooth Muscle Motility (돼지 분만 시기의 조절에 관하여 II. 자궁 평활근의 운동성에 대한 교감신경과 Adrenergic Agonist의 영향)

  • 심철수;이양성;임종옥
    • Korean Journal of Veterinary Service
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    • v.17 no.3
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    • pp.255-263
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    • 1994
  • To elucidate the action of the adrenergic nerve on the isolated uterine smooth muscle of the pig, effects of electrical transmural nerve stimulation and norepinephrine were investigated on the pretreatment of phentolamine ; non-selective ${\alpha}$-adrenoceptor blocker, propranolol ; ${\beta}$-adrenoceptor blocker and the yohimbine;${\alpha}_2$-selective adrenoceptor blocker from physiograph. 1. The relaxation response induced by norepinephrine was the concentration of $10^{-6}$ M at first and maximum response was concentration of $10^{-4}$M. 2. The relaxation response induced by norepinephrine was not effected by the pretreatment with non-selective $\alpha$-adrenoceptor blocker, phentolanune ($10^{-6}$ M) but was completely blocked by the pretreatment with ${\beta}$-adrenoceptor blocker, propranolol($10^{-6}$ M). 3. The contractile response induced by electrical transmural nerve stimulation(20V, 10Hz, 0.5msec, 20sec ) was inhibited by the pretreatment with non-selective ${\alpha}$-adrenoceptor blocker, phentolamine($10^{-6}$ M) but was not inhibited and rather increased by the pretreatment ${\beta}$-adrenoceptor blocker, propranolol($10^{-6}$ M), and was not approximately effected by the pretreatment with ${\alpha}_2$-adrenoceptor blocker, yohimbine($10^{-6}$ M). These finding suggest that it was excitatory action by ${\alpha}_1$-adrenergic nerve and inhibitory action by ${\alpha}_2$-adrenergic, ${\beta}$-adrenergic nerve on uterine smooth muscle of the pig.

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Effects of Alpha 1- and Alpha 2-Adrenoreceptor Stimulation on Galanin mRNA Expression in Primary Cultured Superior Cervical Ganglion Neurons

  • Xing, Yi;Chen, Xiuying;Liu, Zhen;Li, Hao;Liu, Huaxiang;Li, Zhenzhong
    • Biomolecules & Therapeutics
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    • v.19 no.3
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    • pp.315-319
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    • 2011
  • Galanin (Gal) is a 29-amino-acid neuropeptide which is expressed in superior cervical ganglion (SCG) neurons and plays a trophic role in the adult animal and acts as an inhibitory modulator of cholinergic and noradrenergic neurotransmission. Whether activation or inhibition of alpha-adrenoreceptors infl uences Gal mRNA expression in SCG neurons remains unknown. Here, we have evaluated the possible regulation of Gal mRNA expression with acute (4 h) and chronic (4 days) stimulation of alpha 1- and alpha 2-adrenoreceptor agonists or antagonists in primary cultured SCG neurons. The results showed that the amount of Gal mRNA expression in cultured SCG neurons increased signifi cantly after chronic stimulation with alpha 2-adrenoreceptor antagonist yohimbine compared with control SCG neurons at the same time point, whereas the amount of Gal mRNA expression decreased signifi cantly after chronic stimulation with alpha 2-adrenoreceptor agonist clonidine as compared with that in control group. All these effects were not dose-dependent on the administration of alpha 2-adrenoreceptor agonist clonidine or alpha 2-adrenoreceptor antagonist yohimbine. Alpha 1-adrenoreceptor agonist phenylephrine or antagonist prazosin chronic stimulation did not have effects on Gal mRNA expression. Acute exposure of these agents did not have effects on Gal mRNA expression. The present study showed that Gal may be regulated by activation or inhibition of alpha 2-adrenoreceptors, but not alpha 1-adrenoreceptors in sympathetic neurons.

Effects of sympathomimetics on motility in the longitudinal muscle of the cattle rumen (소(牛)의 제1위 종주근 운동성에 대한 교감신경계 약물의 효과)

  • Lim, Hyung-ju;Han, Ho-jae;Han, Bang-keun
    • Korean Journal of Veterinary Research
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    • v.34 no.3
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    • pp.479-486
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    • 1994
  • Effects of catecholamines and the site of receptor of catecholamines were investigated in the longitudinal muscle of the rumen. In order to this experiment, specimens were obtained from 35 Korean Native Cattles, 2-3 years old, in the Kwang-ju area slaughterhouse. Longitudinal muscle strips of rumen were made from sample, and then measured the isometric contraction with physiograph in $37{^{\circ}C}$ organ bath. The results were summarized as follows. 1. 30% of all strips showed rhythmic contraction after short incubation time. 2. Relaxation produced by catecholamines in this preparations increased in a dose-dependant manner. 3. Isoproterenol(${\beta}$-agonist) caused relaxation, but phenylephrine(${\alpha}_1$-agonist) and xylazine(${\alpha}_2$-agonist) were unaffected. 4. The relaxation induced by epinephrine and norepinephrine were not affected by phentolamine(${\alpha}$-blocker) and prazosin(${\alpha}_1$-blocker), yohimbine(${\alpha}_2$-blocker). But propranolol(${\beta}$-antagonist) abolished the effect of catecholamines on relaxation. 5. It is concluded that catecholamines produced relaxation in the longitudinal muscle of rumen via the ${\beta}$-adrenoceptor.

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Oxymetazoline as an ${\alpha}_1-Adrenoceptor$ Agonist -A pressor effect in the rabbit- (${\alpha}_1-Adrenoceptor$ Agonist로서의 Oxymetazoline -가토혈압(家兎血壓) 상승작용(上昇作用)-)

  • Park, Young-Tae;Choi, Soo-Hyung
    • The Korean Journal of Pharmacology
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    • v.18 no.2
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    • pp.59-67
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    • 1982
  • 1) Oxymetazoline, which has been known as an agonist for${\alpha}_1-adrenoceptor$ in various peripheral tissues, caused a pressor response in urethane-anesthetized rabbits when given intra-ventricularly. This pressor response was little affected by pretreatment of rabbits with i.v. guanethidine or chlorisondamine, but it was weakened in rabbits pretreated with either of i.v. phentolamine or guanethidine and chlorisondamine and in guanethidine-pretreated adrenal-ligated rabbits. 2) The pressor to intraventricular oxymetazoline was markedly attenuated by intraventricular pretreatment with prazosin, whereas intraventricular pretreatment with yohimbine or piperoxan did not affect this response. 3) Reserpine-pretreated rabbits also responded with hypertension to intraventricular oxymetazoline, which was markedly diminished by pretreatment with intraventricular prazosin but not affected by yohimbine. 4) Oxymetazoline, given intravenously, produced a pressor response in both whole and spinal rabbits. Intravenous prazosin, phentolamine and yohimbine, in this order, showed greater antagonizing effect to this pressor response. 5) The results indicate that oxymetazoline acts an agonist for ${\alpha}_1-adrenoceptors$ in the rabbit brain participating in the regulation of the blood pressure and in the vasculature of rabbits.

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The Analgesic Effect and the Mechanism of Electroacupuncture on Thermal Hyperalgesia in the Rat Model of Collagenase-induced Arthritis: Mediation by Adrenergic Receptors (Collagenase-induced Arthritis Rat Model에서 Thermal Hyperalgesia에 대한 전침(電鍼)의 진통효과(鎭痛效果) 및 기전연구: Adrenergic Mechanism에 대(對)한 연구(硏究))

  • Seo, Byung-Kwan;Park, Dong-Suk;Baek, Yong-Hyeon
    • Journal of Acupuncture Research
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    • v.28 no.2
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    • pp.57-67
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    • 2011
  • 목적 : Collagenase-induced osteoarthritis(OA) 동물 모델에서 전침의 adrenergic mechanism을 연구하고자 한다. 방법 : Collagenase-induced arthritis(CIA)를 유발하기 위하여 5주령의 male Sprague-Dawley rat의 뒷다리 좌측 무릎 관절에 0.05ml의 4mg/ml collagenase solution을 intra-articular 주입하고, 다시 4일 후에 같은 부위에 같은 농도의 collagenase solution을 intra-articular boosting injection 시행한 뒤, gross, histopathological features 및 biomarker activity 변화를 관찰하였다. 예비실험을 통하여 CIA rat model에서 진통효과를 발휘하는 것으로 확인한, 족삼리(足三里) ($ST_{36}$)에 대한 저빈도 train pulse EA stimulation (2Hz, 0.07 mA, 0.3ms)을 침치료 방법으로 적용하였다. 전침의 진통기전을 확인하기 위하여, ${\alpha}1$-adrenergic antagonist (prazosin, 1 mg/kg, i.p.), ${\alpha}2$-adrenergic receptor antagonist (yohimbine, 2mg/kg, i.p.), ${\alpha}1$-adrenergic receptor agonist(phenylephrine, 2mg/kg, i.p.), ${\alpha}2$-adrenergic receptor agonist(clonidine, $40{\mu}g$/kg, i.p.)을 전침시행 20분 전에 복강 내로 전처치하였다. Tail flick unit(Ugo Basile Model 7360)을 이용하여 열자극에 대한 통증역치를 측정하였다. 결과 : 퇴행성관절염 징후(gross, histopathological features)와 통증역치의 변화가 최대값을 나타내는 CIA 유발 4주차에 저빈도 전침자극(train pulse, 2Hz, 0.07mA, 0.3ms)을 족삼리($ST_{36}$)에 적용하였으며, 족삼리 전침의 진통효과는 ${\alpha}2$-adrenergic receptor antagonist(yohimbine, 2mg/kg, i.p.)전처치에 의해 억제되었으나, ${\alpha}1$-adrenergic antagonist(prazosin, 1 mg/kg, i.p.)전처치에는 억제되지 않았다. 또 ${\alpha}2$-adrenergic receptor agonist(clonidine, $40{\mu}g$/kg, i.p.)의 전처치를 통하여 유의한 synergistic analgesic effect가 관찰되었으나, ${\alpha}1$-adrenergic receptor agonist(phenylephrine, 2mg/kg, i.p.)의 전처치는 전침의 진통효과에 synergistic effect를 미치지 않는 것으로 나타났다. 결론 : 저빈도 족삼리 전침은 CIA로 유발된 염증성 통증에 대하여 진통효과를 발휘하며, 이는 ${\alpha}2$-adrenergic receptor에 의하여 매개되는 것으로 보이며 ${\alpha}1$-adrenergic receptor는 영향을 미치지 않는 것으로 사료된다.

Effects of UK 14,304, An ${\alpha}_2$-Adrenergic Agonist, on Renal Function in Dog (${\alpha}_2$-아드레날린 효능약인 UK 14,304의 신장기능에 미치는 영향)

  • Ko, Suk-Tai;Kim, Hai-Suk;Choi, Hong-Seok
    • YAKHAK HOEJI
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    • v.41 no.4
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    • pp.498-511
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    • 1997
  • The effects of UK 14,304, an ${\alpha}_2$-adrenergic agonist, on renal function were investigated in dogs. UK 14,304, when given intravenousely($15.0{\mu}g/kg,\;50{\mu}g/kg$), produced the increase of urine flow accompanied with the marked augmentation of free water clearance ($C_{H_2O}$) and reabsorption rates of sodium in renal tubules ($R_{Na}$), and the remarkable decrease of osmolar clearance ($C_{osm}$) and the amounts of sodium excreted in urine ($E_{Na}$). UK 14,304 given into a renal artery($1.5{\mu}g/kg,\;5.0{\mu}g/kg$) elicited the increase of urine flow with the augmentation of $C_{H_2O}$ in both kidney. UK 14,304, when administered into carotid artery($3.0{\mu}g/kg,\;10.0{\mu}g/kg$). exhibited the same aspect as shown in intravenous UK 14.304 at smaller dose than the intravenous dose. Diuretic action of intravenous UK 14,304 were produced together with increase of $C_{H_2O}$ in situation of water diuresis too, changes of renal function in this state were the increase of $C_{osm},\;E_{Na},\;and\;E_K$ (excreted amounts of potassium in urine), and the decrease of $R_{Na}\;and\;R_K$, these were different appearances from situation of saline diuresis. Diuretic action of intravenous UK 14,304 were blocked completely by post or pretreatment of yohim-bine, ${\alpha}_2$-adrenergic blocking agents, and inhibited by pretreatment of vasopressin, antidiuretic hormone. Above results suggest that UK 14,304 produces the diuretic action by the inhibition of vasopressin secretion and suppression of electrolytes reabsorption of electrolytes in renal tubules mediated with central ${\alpha}_2$-adrenoceptor in dog.

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Postsynaptic $\alpha_1$-, $\alpha_2$-Adrenoceptors in Rat Isolated Aorta (적출한 흰쥐 대동맥에 있어서 postsynaptic $\alpha_1$-, $\alpha_2$- 아드레날린 수용체에 관한 연구)

  • 임광진;조윤성;고광호;김미영
    • YAKHAK HOEJI
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    • v.30 no.3
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    • pp.157-162
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    • 1986
  • $\alpha$-Adrenoceptor subtypes in the isolated rat aortic strips were examined by using agonists and antagonists which have varying selectivity for $\alpha_1$- and $\alpha_2$- adrenoceptors. Norepinephrine and phenylephrine produced a similar magnitude of maximum contractions. $pA_2$ values for prazosin and yohimbine were not significantly different using norepinephrine or phenylephrine as the agonist, suggesting a single population of alpha-adrenoceptor. Contractile responses produced by alpha-agonists were antagonized more effectively by prazosin (approximately 1000 fold) than by yohimbine.

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Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells

  • Park, Jong-Ju;Seong, Hun-Ki;Kim, Jeong-Soo;Munkhzaya, Byambaragchaa;Kang, Myung-Hwa;Min, Kwan-Sik
    • Development and Reproduction
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    • v.21 no.2
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    • pp.111-120
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    • 2017
  • Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG ($eCG{\beta}/{\alpha}$) and mutant eCG ($eCG{\beta}/{\alpha}{\Delta}56$) with an N-linked oligosaccharide at $Asn^{56}$ of the ${\alpha}-subunit$. Both the rec-eCGs were obtained from CHO-K1 cells. The agonist activation of receptors was analyzed by measuring stimulation time and concentrations of rec-eCGs. Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of $rec-eCG{\beta}/{\alpha}$. The dose-dependent response was highest when 10 ng of $rec-eCG{\beta}/{\alpha}$ was used. The deglycosylated $eCG{\beta}/{\alpha}{\Delta}56$ mutant did not enhance the agonist-stimulated internalization. We concluded that the state of activation of rFSHR and rLH/CGR could be modulated through agonist-stimulated internalization. Our results suggested that the eLH/CGRs are mostly internalized within 60 min by agonist-stimulation by rec-eCG. We also suggested that the lack of responsiveness of the deglycosylated $eCG{\beta}/{\alpha}{\Delta}56$ was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR.

The Role of Central Postsynaptic ${\alpha}_2$-Adrenoceptor on the Immobility Duration in the Forced-swimming Test Mice (새앙쥐 강제수영시 부동자세 시간에 대한 Central postsynaptic ${\alpha}_2$-Adrenoceptor의 역할에 대한 연구)

  • Rhim, Byung-Yong;Kim, Sang-Kon;Lee, Won-Suk;Hong, Ki-Whan
    • The Korean Journal of Pharmacology
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    • v.21 no.2
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    • pp.90-98
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    • 1985
  • 1) In the study of the forced-swimming test in mice (FSM), the duration of immobility posture was dose-dependently shortened by ${\alpha}_2$-agonists, clonidine and guanabenz. BH-T 933 and oxymetazoline also decreased it . Xylazine rather increased the immobility duration at low dose. 2) ${\alpha}_1$-Agonists, cirazoline, amidephrine and methoxamine, however, showed inconsistent effect on the immobility duration (ID). 3) The decrease in ID by clonidine and guanabenz was antagonized by pretreatment with yohimbine, idazoxan and phentolamine (${\alpha}_2$antagonist), but not by prazosin and corynanthine (${\alpha}_1$-antagonist) .4) The ID in the FSM was shortened dose-dependently by d-amphetamine, and it was also antagonized by yohimbine, but not by prazosin. 5) In the mice pretreated with either ${\alpha}$-methyl-p-tyrosine or reserpine, or with combination of both, the decrease in ID was still evoked by clonidine. 6) When the mice were chronically treated with antidepressants (desipramine and imipramine), or with electroconvulsive shock, clonidine still decreased the ID as it did in the control. 7) These results provided the evidences to hypothesize that the change of the ID in the FSM is closely related with the postsynaptie ${\alpha}_2$-adrenoceptor located on the central noradrenergic neuron body. Furthermore, it is assumed that this escape-directed behavior enhanced by ${\alpha}_2$-adrenoceptor agonist may be the result in some analogy with the incentive of drives which are directed toward the self-preservation.

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