• The Korean Journal of Physiology and Pharmacology
• /
• 제1권5호
• /
• pp.485-493
• /
• 1997

We investigated the effect of ${\alpha}-adrenergic$ and cholinergic receptor agonists on $Ca^{2+}$ current in adult rat trigeminal ganglion neurons using whole-cell patch clamp methods. The application of acetylcholine, carbachol, and oxotremorine ($50\;{\mu}M\;each$) produced a rapid and reversible reduction of the $Ca^{2+}$ current by $17{\pm}6%,\;19{\pm}3%,\;and\;18{\pm}4%$, respectively. Atropine, a muscarinic antagonist, blocked carbachol- induced $Ca^{2+}$ current inhibition to $3{\pm}1%$. Norepinephrine ($50\;{\mu}M$) reduced $Ca^{2+}$ current by $18{\pm}2%$, while clonidine ($50\;{\mu}M$), an ${\alpha}2-adrenergic$ receptor agonist, inhibited $Ca^{2+}$ current by only $4{\pm}1%$. Yohimbine, an ${\alpha}2-adrenergic$ receptor antagonist, did not block the inhibitory effect of norepinephrine on $Ca^{2+}$ current, whereas prazosin, an ${\alpha}1-adrenergic$ receptor antagonist, attenuated the inhibitory effect of norepinephrine on $Ca^{2+}$ current to $6{\pm}1%$. This pharmacology contrasts with ${\alpha}2-adrenergic$ receptor modulation of $Ca^{2+}$ channels in rat sympathetic neurons, which is sensitive to clonidine and blocked by yohimbine. Our data suggest that the modulation of voltage dependent $Ca^{2+}$ channel by norepinephrine is mediated via an α1-adrenergic receptor. Pretreatment with pertussis toxin (250 ng/ml) for 16 h greatly reduced norepinephrine- and carbachol-induced $Ca^{2+}$ current inhibition from $17{\pm}3%\;and\;18{\pm}3%\;to\;2{\pm}1%\;and\;2{\pm}1%$, respectively. These results demonstrate that norepinephrine, through an ${\alpha}1-adrenergic$ receptor, and carbachol, through a muscarinic receptor, inhibit $Ca^{2+}$ currents in adult rat trigeminal ganglion neurons via pertussis toxin sensitive GTP-binding proteins.

• Journal of Acupuncture Research
• /
• 제28권2호
• /
• pp.57-67
• /
• 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.

• The Korean Journal of Physiology
• /
• 제29권2호
• /
• pp.203-216
• /
• 1995

The effects of ${\alpha}_1-adrenergic$ receptor stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force were investigated in ventricular muscles from guinea-pig hearts. Action potentials, intracellular $Na^+$ activity, and twitch force of ventricular papillary muscles were measured simultaneously under various experimental conditions. Stimulation of the ${\alpha}_1-adrenergic$ receptor by phenylephrine produced variable changes in action potential duration, a slight hyperpolarization of the diastolic membrane potential, a decrease in intracellular $Na^+$ activity, and a biphasic inotropic response in which a transient negative inotropic response was followed by a sustained positive inotropic response. These changes were blocked by prazosin, an antagonist of the ${\alpha}_1-adrenergic$ receptor, but not by atenolol, an antagonist of the ${\beta}-adrenergic$ receptor. This indicates that the changes in membrane potential, intracellular $Na^+$ activity, and twitch force are mediated by stimulation of the ${\alpha}_1-adrenergic$ receptor, but not by stimulation of ${\beta}-adrenergic$ receptor. The decrease in intracellular $Na^+$ activity was not observed in quiescent muscles, depending on the rate of the action pontentials in beating muscles. The intracellular $Na^+$ activity decrease was substantially inhibited by tetrodotoxin. However, the decrease in intracellular $Na^+$ activity was not affected by an inhibition of the $Na^+-K^+$ pump. Therefore, the decrease in intracellular $Na^+$ activity mediated by the ${\alpha}_1-adrenergic$ receptor appears to be due to a reduction of $Na^+$ influx during the action potential, perhaps through tetrodotoxin sensitive $Na^+$ channels. Our study also revealed that the decrease in intracellular $Na^+$ activity might be related to the transient negative inotropic response. The intracellular $Na^+$ activity decrease could lower intracellular $Ca^{2+}$ through the $Na^+-Ca^{2+}$ exchanger and thereby produce a decline in twitch force.

• The Korean Journal of Physiology and Pharmacology
• /
• 제2권6호
• /
• pp.753-761
• /
• 1998

Preconditioning of a heart with small doses of catecholamines induces a tolerance against the subsequent lethal ischemia. The present study was performed to find a specific receptor pathway involved with the catecholamine preconditioning and to test if adenosine plays a role in this cardioprotective effect. Isolated rat hearts, pretreated with small doses of ${\alpha}-\;or\;{\beta}-adrenergic$ agonists/antagonists, were subjected to 20 minutes ischemia and 20 minutes reperfusion by Langendorff perfusion method. Cardiac mechanical functions, lactate dehydrogenase and adenosine release from the hearts were measured before and after the drug treatments and ischemia. In another series of experiments, adenosine $A_1\;or\;A_2$ receptor blockers were treated prior to administration of adrenergic agonists. Pretreatments of a ${\beta}-agonist,\;isoproterenol(10^{-9}{\sim}10^{-7}\;M)$ markedly improved the post-ischemic mechanical function and reduced the lactate dehydrogenase release. Similar cardioprotective effect was observed with an ?-agonist, phenylephrine pretreatment, but much higher $concentration(10^{-4}\;M)$ was needed to achieve the same degree of cardioprotection. The cardioprotective effects of isoproterenol and phenylephrine pretreatments were blocked by a ${\beta}_1-adrenergic$ receptor antagonist, atenolol, but not by an ${\alpha}_1-antagonist,$ prazosin. Adenosine release from the heart was increased by isoproterenol, and the increase was also blocked by atenolol, but not by prazosin. A selective $A_1-adenosine$ receptor antagonist, 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) blocked the cardioprotection by isoproterenol pretreatment. These results suggest that catecholamine pretreatment protects rat myocardium against ischemia and reperfusion injury by mediation of ${\beta}_1-adrenergic$ receptor pathway, and that adenosine is involved in this cardioprotective effect.

• The Korean Journal of Pain
• /
• 제9권2호
• /
• pp.318-325
• /
• 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.

• 한국어류학회지
• /
• 제12권1호
• /
• pp.38-45
• /
• 2000

어종에 따라 혈관의 긴장도 조절은 다양한 신경전달물질에 의하여 조절되고 있다. 그러나 아직 대부분의 어종에서 자율신경계 신경전달물질 및 혈관긴장도 조절인자들의 기능에 대하여 명확하게 규명되어 있지 않다. 본 연구는 아직 연구되지 않은 분야인 이스라엘잉어에서의 자율신경계 신경전달물질들의 혈관긴장도 조절에서의 역할을 규명하고자 적출복대동맥을 이용하여 시험하였다. 이 적출혈관에서 아세틸콜린 (ACh)은 정상혈관과 미리 일정수준 수축시킨 혈관 모두에서 수축을 유발하였으며 수축작용은 무스카린성 길항제인 아트로핀에 의해 거의 완벽하게 차단되었다. 여러 가지 아드레날린성 수용체를 동시에 흥분시키는 내인성 물질인 에피네프린 (Epi)은 혈관의 조건에 상관없이 이완반응을 유발하였다. 그러나 유사한 내인성물질인 노르에피네프린 (NE)은 정상혈관에서는 미약한 수축율, 미리수축된 혈관에서는 이완작용을 유발하였다. 한편 ${\alpha}_1$ 아드레날린성 수용체 흥분제인 페닐에프린은 수축을, $\beta$수용체 홍분제인 이소프로테레놀은 이완을 각각 유발하였으며 ${\alpha}_2$수용체 흥분제인 클로니딘은 아무런 반응을 유발하지 않았다. Epi, NE 및 이소프로테레놀에 의해 유발된 혈관이완 반응은 $\beta$ 아드레날린성 수용체 길항제인 프로프라놀롤에 의해 유의하게 억제되었다. 따라서 살아있는 상태의 이스라엘 잉어에서는 ACh는 주로 무스카린성 수용체 활성화에 의한 혈관을 수축하는 기능을, Epi과 NE는 $\beta$수용체 흥분에 의한 이완작용을 각각 발휘하는 것으로 판단된다.

• Journal of Acupuncture Research
• /
• 제20권2호
• /
• pp.85-97
• /
• 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.

• 한국패류학회지
• /
• 제25권1호
• /
• pp.15-22
• /
• 2009

Because it is known that bivalve hearts contain various modulatory systems activated by neuroendocrine substances, it was examined whether different classes of endogenous and synthetic drugs of neuroendocrinological importance can influence cardiac functions of the Pacific oyster Crassostrea gigas. Cholinergically active agents acetylcholine and carbachol increased heart rates while diminishing cardiac contractility. Adrenergically active substances norepinephrine (NE) and epinephrine (Epi) also induced heart rate increase and contractility decrease. An $\alpha_1$-adrenergic receptor-selective agonist phenyephrine (PE) failed to modulate either parameter. The Epi-induced heart rate increase and contractile depression were both blocked significantly by non-selective $\beta_1/\beta_2$-adrenergic antagonist propranolol. A $\beta_1$-selective antagonist atenolol prevented Epi-induced heart rate decrease but not the contractile depression, suggesting possible $\beta_2$ receptors for Epi-induced contractile depression. The three autacoids examined exerted discrete responses: histamine increased heart rate and depressed contraction; $\gamma$-amino-butyric acid increased both parameters; serotonin failed to change either parameter. The 5 piscine anesthetic agents examined, MS-222, benzocaine, quinaldine, urethane, pantocaine and pentobarbital, all failed to influence the cardiac function of oysters. Collectively, activities of neuroendocrinologically acting agents in mammals showed unexpected and distinct activities from those in mammalian cardiovascular systems. These results obtained from substances of different physiological functions can serve as a basis for understanding neuroendocrine control of the heart function in Pacific oyster.

• 대한수의학회지
• /
• 제35권2호
• /
• pp.237-243
• /
• 1995

The effects of various autonomic blocking agents to perivascular nerve stimulation were investigated on isolated coronary artery of pig. 1. The magnitude of contractile response to perivascular nerve stimulation increased with increasing frequency(280Hz) of stimulation. 2. The contractions to perivascular nerve stimulation(40V, 40Hz, 0.5msec, 1min) were increased by pretreatment of the cholinestrase inhibitor, physostigmine. 3. The contraction to perivascular nerve stimulation(40V, 40Hz, 0.5msec, 1min) was antagonised by the muscarinic antagonist, atropine. 4. The contraction to perivascular nerve stimulation(40V, 40Hz, 0.5msec, 1min) was blocked by the neural blocker, tetrodotoxin. 5. The contractions to perivascular nerve stimulation(40V, 40Hz, 0.5msec, 1min) were not significantly affected by the ${\alpha}$-adrenergic antagonist, phentolamine or ${\beta}$-adrenergic antagonist, propranolol. 6. The contractile response by the acetylcholine was increased by the pretreatment of cholinestrase inhibitor, physostigmine. This findings suggest that the powerful excitatory action by the perivascular nerve stimulation may be linked to muscarinic receptor by cholinergic nerve excitation in coronary artery of pig.

• Journal of Acupuncture Research
• /
• 제22권1호
• /
• pp.99-108
• /
• 2005

Collagen 유발(誘發) 관절염(關節炎) 동물모델을 이용하여 족삼리(足三里) (ST36) 봉독약월(蜂毒藥鉞)의 진통효과(鎭痛效果)와 그 기전(機轉) 을 관찰하기 위하여 TFL을 지표로 하여 통증 역치의 변화와 naloxone 및 yohimbine으로 전처(前處) 치한(置) 후 (後) 봉독약침(蜂毒藥鍼)의 진통효과(鎭痛效果)를 관찰한 결과 다음과 같은 결론을 얻었다. 1. Collagen 유발(誘發) 관절염(關節炎)의 rat에서 TFL 통증 역치는 1, 2, 3 및 4주로 갈수록 지속적 감소를 나타내었다. 2. 1회와 2주간 봉독약철(蜂毒藥鐵)은 collagen 유발(誘發) 관절염(關節炎) rat의 통증역치를 각각 증가시켰다. 3. CIA rat에 opioid receptor antagonist인 naloxone을 투여한 후 봉독약침(蜂毒藥鍼)을 처치한 결과 진통효과(鎭痛效果)가 유지되는 것으로 보아 봉독약광(蜂毒藥鑛)의 진통기전(鎭痛機轉)은 아편양 기전(機轉)과 관련이 없는 것으로 사료된다. 4. CIA rat에 ${\alpha}2$-adrenoceptor antagonist인 ohimbine을 투여한 후 봉독약침(蜂毒藥鍼)을 처치한 결과 진통효과(鎭痛效果)가 길항(拮抗)되는 것으로 보아, 봉독약침(蜂毒藥鍼)의 기전(機轉)은 ${\alpha}2$-adrenoceptor에 의하여 매개는 것으로 사료된다.