• Archives of Pharmacal Research
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• v.9 no.4
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• pp.219-222
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• 1986

Dose-dependent increasesin blood glucose were produced by epinephrine and clonidine in fasted male mice. Isoproterenol was ineffective in increasing blood glucose at lower doses ($10^{-8}M$/kg-$10^{-7}M$/kg); with higher dose ($10^{-6}M$/kg) the glucose level was increased. The hyperglycemia induced by epinephrine was inhibited by yobimbine, prazosin and propranolol, indicating that the hyperglycemic effect of epinephrine is mediated by alpha-1, alpha-2 and beta adrenoceptor. When clonidine (10$^{-6}$ M/kg) was administered simultaneously with sioproterenol ($10^{-6}M$/kg), an enhenced hyperglycemic effect was observed. The increment produced by clonidine plus isoproterenol was higher than that by clonidine alone. These increment produced by clonidine plus isoproterenol was higher than that by clonidine alone. These results suggest that stimulation of alpha-2 adrenoceptor may be reponsible for the exertion of the hyperglycemic effect by beta agonists in fasted mice.

• The Korean Journal of Pharmacology
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• v.22 no.1 s.38
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• pp.24-33
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• 1986

To ascertain the existence of various adrenoceptors involved in active transport of sodium in the frog skin and to delineate their physiological roles, the influence of various adrenergic agonists and antagonists on the potential difference (PD), short-circuit current (SCC) and total skin conductance (TSC) of the isolated frog skin of Rana nigromaculata were investigated. PD and SCC were determined with Ussing's technique. Drugs were administered to the serosal side of the skin. Experimental results were summarized as follows: 1. The responses to norepinephrine (NE, $6{\times}10^{-8}-6{\times}10^{-5})M$), phenylephrine (PE, $5{\times}10^{-6}-5{\times}10^{-4}M$) and epinephrine (Epi, $5.5{\times}10^{-7}-5.5{\times}10^{-5}M$) were characterized by marked elevation of PD & SCC in dose-related fashion, but the maximal effect attained by Epi was less than those of NE and PE. 2. These increments of PD & SCC were significantly inhibited by prazosin $(2{\times}10^{-6}M)$, a speciflc ${\alpha}_1$-adrenoceptor blocker. The stimulatory effect on PD & SCC were completely abolished by phenoxybenzamine (PBZ, $3.3{\times}10^{-5}M$), an irreversible ${\alpha}$-adrenoceptor blocking agent. Furthermore, with a larger doses of Epi produced marked decline of PD & SCC after the PBZ pretreatment. 3. Isoproterenol (ISP), a ${\beta}$-adrenoceptor agonist, in concentrations ranging from $5{\times}10^{-7}$ to $5{\times}10^{-6}M$ produced dose-related decrease in PD & SCC, which could be abolished by pretreatment with propranolol $(4{\times}10^{-6}M)$, a specific ${\beta}$-adrenoceptor blocker. It was further noted that the effects of Epi on PD & SCC were markedly potentiated by Propranolol pretreatment. 4. Clonidine as well as guanabenz produced increases in PD & SCC and these effects were inhibited more specifically by prazosin pretreatment than by yohimbine. These results indicated that there exist in the frog skin two distinctive types of adrenoceptors, ${\alpha}$ and ${\beta}$, which roughly corresponds to those in mammals, and that the ${\alpha}$ type of adrenoceptors mediate the stimulation of PD & SCC, whereas ${\beta}$-adrenoceptors mediate the inhibition. However, based on evidence at hand, no conclusion could be drawn on the subtype of ${\alpha}$-adrenoceptors which is involved in the stimulation of sodium transport in the frog skin.

• 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.

• Asian-Australasian Journal of Animal Sciences
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• v.7 no.3
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• pp.397-400
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• 1994

The effect of xylazine administration on plasma cortisol, prolactin, glucose and packed cell volume (PCV) responses to immobilization and heat stress was investigated. Immobilization of rats for 2 hours by ligation of the fore and hind legs strongly caused approximately two-fold increase in plasma cortisol and prolactin levels. Plasma glucose and PCV were not significantly changed. Pretreatment of immobilized rats with xylazine (20 mg/kg body weight i.m.) resulted in approximately 20% reduction in both plasma cortisol and prolactin concentrations. A marked hyperglycemia and increase in the PCV value was observed. On the other hand, rats exposed to acute heat stress ($40^{\circ}C$, and 60% relative humidity) for 2 hours, also developed two fold increase in both plasma cortisol and prolactin concentrations and the pretreatment with xylazine caused a 20% reduction in the levels of both hormones. Plasma glucose level was not significantly changed in heat stressed rats but it was markedly increased after pretreatment with xylazine. PCV was significantly incrcased under heat stress and pretreatment with xylazine induced a pronounced elevation in this value. It was suggested that stimulation of cortisol and prolactin secretion in response to immobilization or heat stress can be partially reduced by an alpha 2-adrenergic agonist.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.6
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• pp.753-761
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• 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.

• Korean Journal of Biological Psychiatry
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• v.7 no.1
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• pp.80-84
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• 2000

Background : Hypersalivation can be a troublesome side effect of clozapine, limiting its usefulness in the management of some cases of schizophrenia. But the pharmacodynamic basis of clozapine-induced hypersalivation remains obscure. Object : The aim of this study was to evaluate the effect of the ${\alpha}_2$-adrenergic agonist clonidine on clozapine-induced hypersalivation in the patients who were receiving clozapine. Method : Twenty one schizophrenic inpatients on clozapine participated in the study. The amount of saliva was measured on the 7th day at 8pm after starting clozapine treatment. Of them, 15 patients who had experienced hypersalivation was treated with 0.1mg/day of clonidine. Result : Of 21 schizophrenic patients treated with clozapine in the psychiatric inpatient clinic, 15(71.4%) complained hypervalivation. After clonidine treatment, mean salivary flow-rate was decreased significantly in these patients. Conclusion : Clozapine-induced hypersalivation could be decreased by administration of ${\alpha}_2$-adrenergic agonist clonidine and compliance could be improved. Also our study supports the notion that increased adrenergic tone contributes to clozapine-induced hypersalivation.

• Proceedings of the Korean Biophysical Society Conference
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• 1997.07a
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• pp.27-27
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• 1997

The effects of $a_1$-adrenoceptor stimulation on intracellular $Ca^{2+}$ ([C $a^{2+}$]$_{i}$ ) transient, contraction, and L-type $Ca^{2＋}$ current ( $I_{Ca,L}$) were studied in single cells isolated from ventricles of guinea pig hearts. Phenylephrine, $\alpha$$_1$-adrenergic agonist, (5$\times$10$^{-5}$ ~10$^{-4}$ M) produced a biphasic pattern of inotropism： transient negative response (decrease in contraction by 23.9$\pm$2.5% of control) followed by a sustained positive response (increase in contraction by 60.0$\pm$3.4%, mean $\pm$ SD, n=12).(omitted)ted)

• Journal of Dental Anesthesia and Pain Medicine
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• v.19 no.2
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• pp.83-90
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• 2019

Dexmedetomidine is a highly selective ${\alpha}2$-adrenoceptor agonist with a vast array of properties, making it suitable for sedation in numerous clinical scenarios. Its use was previously restricted to the sedation of intensive care unit patients. However, its use in pediatric dental sedation has been gaining momentum, owing to its high suitability when compared with conventional pediatric sedatives. Its properties range from sedation to anxiolysis to analgesia, due to its sympatholytic properties and minimal respiratory depression ability. Because dexmedetomidine is an efficacious and safe drug, it is gaining importance in pediatric sedation. Thus, the aim of this review is to highlight the properties of dexmedetomidine, its administration routes, its advantages over the commonly used pediatric sedatives, and especially its role as an alternative pediatric sedative.

• Journal of The Korean Society of Clinical Toxicology
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• v.5 no.2
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• pp.123-125
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• 2007

Amitraz is a formamidine-derived insecticide and acaricide which is commonly used throughout the world. Amitraz intoxication is mediated through ${\alpha}_2$ adrenergic receptor agonist effects, similar to those of the ${\alpha}_2$ agonist clonidine. We report a case of a patient who experienced coma and hypotension after amitraz ingestion. A 37-year-old woman visited the ER with symptoms of vomiting and altered mental state. She had ingested a mouthful of liquid amitraz concentrate (12.5%), which rapidly led to vomiting, hypotension, bradycardia, hyperglycemia, and mental stupor. Supportive treatment, including mechanical ventilation and administration of inotropics, resulted in full recovery within four days.

• Biomolecules & Therapeutics
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• v.4 no.1
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• pp.103-109
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• 1996

To investigate the effect of the third intracellular loop (i3 loop) peptide of human $\beta$$_2$-adrenergic receptor on receptor agonist binding, we expressed third intracellular loop region of human $\beta$$_2$-adrenergic receptor as glutathione S-transferase fusion protein in E. coli. DNA fragment of the receptor gene which encodes amino acid 221-274 of human $\beta$$_2$-adrenergic receptor was amplified by polymerase chain reaction and subcloned into the bacterial fusion protein expression vector pGEX-CS and expressed as a form of glutathione-S-transferase (GST) fusion protein in E. coli DH5$\alpha$. The receptor fusion protein was identified by SDS-PAGE and Western blot using monoclonal anti-GST antibody. The fusion protein expressed in this study was purified to an apparent homogeneity by glutathione Sepharose CL-4B affinity chromatography. The purified i3 loop fusion proteins at a concentration of 10 $\mu\textrm{g}$/ι caused right shift of the isoproterenol competition curve of [$^3$H]Dihydroalprenolol binding to hamster lung $\beta$$_2$-adrenergic receptor indicating lowered affinity of isoproterenol to $\beta$$_2$-adrenergic receptor possibly due to the uncoupling of receptor and G protein in the presence of the fusion protein. The uncoupling of receptor and G protein suggests that i3 loop region plays a critical role on $\beta$$_2$-adrenergic receptor G protein coupling.