• 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.27 no.4
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• pp.313-320
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• 2014

Dexmedetomidine, an imidazoline compound, is a highly selective ${\alpha}_2$-adrenoceptor agonist with sympatholytic, sedative, amnestic, and analgesic properties. In order to minimize the patients' pain and anxiety during minimally invasive spine surgery (MISS) when compared to conventional surgery under general anesthesia, an adequate conscious sedation (CS) or monitored anesthetic care (MAC) should be provided. Commonly used intravenous sedatives and hypnotics, such as midazolam and propofol, are not suitable for operations in a prone position due to undesired respiratory depression. Dexmedetomidine converges on an endogenous non-rapid eye movement (NREM) sleep-promoting pathway to exert its sedative effects. The great merit of dexmedetomidine for CS or MAC is the ability of the operator to recognize nerve damage during percutaneous endoscopic lumbar discectomy, a representative MISS. However, there are 2 shortcomings for dexmedetomidine in MISS: hypotension/bradycardia and delayed emergence. Its hypotension/bradycardiac effects can be prevented by ketamine intraoperatively. Using atipamezole (an ${\alpha}_2$-adrenoceptor antagonist) might allow doctors to control the rate of recovery from procedural sedation in the future. MAC, with other analgesics such as ketorolac and opioids, creates ideal conditions for MISS. In conclusion, dexmedetomidine provides a favorable surgical condition in patients receiving MISS in a prone position due to its unique properties of conscious sedation followed by unconscious hypnosis with analgesia. However, no respiratory depression occurs based on the dexmedetomidine-related endogenous sleep pathways involves the inhibition of the locus coeruleus in the pons, which facilitates VLPO firing in the anterior hypothalamus.

• Molecules and Cells
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• v.37 no.8
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• pp.585-591
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• 2014

The ${\beta}_2$ adrenergic receptor (ADRB2) is a G protein-coupled transmembrane receptor expressed in the human respiratory tract and widely recognized as a pharmacological target for treatments of asthma and chronic obstructive pulmonary disorder (COPD). Although a number of ADRB2 agonists have been developed for use in asthma therapy, indacaterol is the only ultra-long-acting inhaled ${\beta}_2$-agonist (LABA) approved by the FDA for relieving the symptoms in COPD patients. The precise molecular mechanism underlying the pharmacological effect of indacaterol, however, remains unclear. Here, we show that ${\beta}$-arrestin-2 mediates the internalization of ADRB2 following indacaterol treatment. Moreover, we demonstrate that indacaterol significantly inhibits tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-induced NF-${\kappa}B$ activity by reducing levels of both phosphorylated-IKK and -$I{\kappa}B{\alpha}$, thereby decreasing NF-${\kappa}B$ nuclear translocation and the expression of MMP-9, an NF-${\kappa}B$ target gene. Subsequently, we show that indacaterol significantly inhibits TNF-${\alpha}$/NF-${\kappa}B$-induced cell invasiveness and migration in a human cancer cell line. In conclusion, we propose that indacaterol may inhibit NF-${\kappa}B$ activity in a ${\beta}$-arrestin2-dependent manner, preventing further lung damage and improving lung function in COPD patients.

• The Korean Journal of Pharmacology
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• v.19 no.2
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• pp.1-8
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• 1983

Prostaglandin(PG) is ubiquitously distributed in most mammalian tissue and their actions are complicated. Especially in autonomic nervous system, there are evidences indicating that PGs act as neuromodulators i.e., PGs, which are released in the vicinity of autonomic neuroeffector junctions, influence the release and the response of the neurotransmitter. Present study was undertaken to elucidate the interrelationship between $PGF_{2\alpha}$ and adrenergic ${\alpha}_2-receptor$ function in electrical field stimulation induced contractile response of vas deferens in rat. Male rat, weighing 150{\sim}200\;g, was sacrificed and vas deferens was obtained. The isolated vas deferens strip was placed between two platinum electrodes in temperature controlled $(37^{\circ}C)$ muscle chamber containing Tyrode's solution and the electrical field stimulation(EFS) induced contraction was recorded with Grass Polygraph(Model 7) via force displacement transducer (FT .03, Grass). The results are summarized as follows: 1) Electrical field stimulation for 1sec( 1 msec, 40 cps) induced contraction of vas deferens was completely blocked by tetrodotoxin. 2) Bretylium caused marked inhibition of the EFS-induced contraction, hut tyramine and cocaine augmented the contraction. 3) EFS-induced contraction was inhibited or little affected in distal portion of vas deferens by norepinephrine or methoxamine, but the contraction was rather augmented by the ${\alpha}-agonists$ in proximal portion. 4) Clonidine inhibited the EFS-induced contraction proportionally to the concentration in distal portion, which was blocked by yohimbine pretreatment, but in the presence of $PGF_{2\alpha}$ the blockade by yohimbine was reversed. 5) Indomethacin pretreatment reduced the effect of clonidine, but addition of $PGF_{2\alpha}$ after washing-out the indomethacin caused the contraction to the control level. From these results it is suggested that PG synthesis is a necessary step and the PG itself has a permissive role in ${\alpha}_2-adrenoceptor$ action in rat vas deferens.

• Journal of Audiology & Otology
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• v.23 no.2
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• pp.89-95
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• 2019

Background and Objectives: Knowing the ototoxic potential of the agents used in medical treatments is important for the protection of hearing. Although we have knowledge regarding some effects of dexmedetomidine, which is an anesthetic-sparing drug, its influence over the hearing system has never been studied and is obscure yet. The aim of this study is to determine the effects of intravenous dexmedetomidine application during sevoflurane anesthesia on otoacoustic emissions (OAEs). Subjects and Methods: This prospective randomized study was performed on 60 patients (34 male, 26 female, mean age: 30.6±9.2 years) who were scheduled for an elective surgery under general anesthesia and the patients were enrolled and randomly divided into 2 groups. They received dexmedetomidine (Group D) or Saline (Group S) infusion during a standardized Sevoflurane anesthesia. Transient and distortion product OAEs were measured preoperatively and postoperatively (24th hour). OAE results were compared within and between groups. Results: In group D postoperative OAEs were lower than preoperative OAEs and postoperative levels of group S, especially at low frequencies (p<0.05). Conclusions: Dexmedetomidine infusion affects the micromechanical function of cochlea especially in the low-frequency region. Dexmedetomidine should be carefully used during general anesthesia to avoid its probable harmful effects on cochlear micromechanics.

• Korean Journal of Audiology
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• v.23 no.2
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• pp.89-95
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• 2019

Background and Objectives: Knowing the ototoxic potential of the agents used in medical treatments is important for the protection of hearing. Although we have knowledge regarding some effects of dexmedetomidine, which is an anesthetic-sparing drug, its influence over the hearing system has never been studied and is obscure yet. The aim of this study is to determine the effects of intravenous dexmedetomidine application during sevoflurane anesthesia on otoacoustic emissions (OAEs). Subjects and Methods: This prospective randomized study was performed on 60 patients (34 male, 26 female, mean age: 30.6±9.2 years) who were scheduled for an elective surgery under general anesthesia and the patients were enrolled and randomly divided into 2 groups. They received dexmedetomidine (Group D) or Saline (Group S) infusion during a standardized Sevoflurane anesthesia. Transient and distortion product OAEs were measured preoperatively and postoperatively (24th hour). OAE results were compared within and between groups. Results: In group D postoperative OAEs were lower than preoperative OAEs and postoperative levels of group S, especially at low frequencies (p<0.05). Conclusions: Dexmedetomidine infusion affects the micromechanical function of cochlea especially in the low-frequency region. Dexmedetomidine should be carefully used during general anesthesia to avoid its probable harmful effects on cochlear micromechanics.

• The Korean Journal of Pharmacology
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• v.24 no.2
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• pp.153-164
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• 1988

The potential role of endogenous opioid peptides (EOPS) in cardiovascular regulation has only recently been entertained. EOPS have been localized in brain, spinal cord, autonomic ganglia, particularly the adrenal gland, and many other peripheral tissues. There are at least five major types of opioid receptors; namely ${\mu},\;{\delta},\;k,\;{\sigma},\;and\;{\varepsilon}$ and Experimental evidence indicates that cardiovascular actions of the peptide are mediated primarily by ${\mu},\;{\delta}$ and k receptors, and that these receptor types may be allosterically coupled. In anesthetized rabbits met-enkephalin decreased blood pressure and heart rate, which closely paralleled a reduction in sympathetic discharge. Naloxone, but not naloxone methobromide, antagonized these effects, which suggests a central site of action of met-enkephalin. A number of autonomic agents, particularly adrenergic ${\alpha}$-and, ${\beta}-agonists$ and antagonists modify the cardiovascular actions of met-enkephalin. Experiments in reserpine-treated and adrenalectomized rats provide no evidence of sympathetic nervous system involvement in the pressor responses to intravenous injection of opioid peptides, but rather suggest a direct peripheral action. Finally, activation of a beta-endorphinergic pathway projecting from the arcuate nucleus to the nucleus tractos solitarii in rats can cause naloxone reversible hypotension and bradycardia. There is evidence to implicate this pathway in antihypertensive drug action and in the modulation of baroreflex activity.