• Title/Summary/Keyword: alpha-2 agonist

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Clonidine Added to Lidocaine Prolongs the Duration of Anesthesia and Analgesia during Brachial Plexus Block (Lidocaine을 사용한 상박신경총 차단시 Clonidine을 첨가하면 마취와 제통시간이 연장된다)

  • Kim, Tae-Hwan
    • The Korean Journal of Pain
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    • v.14 no.1
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    • pp.41-45
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    • 2001
  • Background: Clonidine, a selective ${\alpha}_2$ adrenergic agonist, increases the duration of anesthesia and analgesia when it is used with local anesthetics. This study was undertaken to evaluate whether clonidine, which was mixed with lidocaine for the brachial plexus block (BPB), has a local (peripheral) or a systemic (central) anesthetic effect. Methods: Seventy patients scheduled for upper extremity surgery were randomly allocated to two groups. In group IV (n = 35) an axillary perivascular BPB was performed with 40 ml of 1% lidocaine and 1:200,000 epinephrine, and just after BPB clonidine $2{\mu}g/kg$ was administered intravenously. In group BPB (n = 35) the same BPB was performed with 40 ml of 1% lidocaine, 1:200,000 epinephrine and clonidine $2{\mu}g/kg$. The following variables were recorded: onset time, duration of anesthesia and analgesia, and adverse effects. Results: Onset time was comparable in both groups. The duration of anesthesia and analgesia significantly increased to 306 min and 354 min in group BPB, when compared to 119 min and 151 min in group IV, respectively. No side effects such as hypotension, bradycardia, and sedation were reported. Conclusions: The duration of anesthesia and analgesia is prolonged by adding clonidine to lidocaine during brachial plexus block, which suggests that its effect is local rather than systemic.

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Diarylpropionitrile inhibits melanogenesis via protein kinase A/cAMP-response element-binding protein/microphthalmiaassociated transcription factor signaling pathway in α-MSH-stimulated B16F10 melanoma cells

  • Lee, Hyun Jeong;An, Sungkwan;Bae, Seunghee;Lee, Jae Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.2
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    • pp.113-123
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    • 2022
  • Diarylpropionitrile (DPN), a selective agonist for estrogen receptor β (ERβ), has been reported to regulate various hormonal responses through activation of ERβ in tissues including the mammary gland and brain. However, the effect of DPN on melanogenesis independent of ERβ has not been studied. The aim of this study is to examine the possibility of anti-melanogenic effect of DPN and its underlying mechanism. Melanin contents and cellular tyrosinase activity assay indicated that DPN inhibited melanin biosynthesis in alpha-melanocyte stimulating hormone-stimulated B16F10 melanoma cell line. However, DPN had no direct influence on in vitro tyrosinase catalytic activity. On the other hand, 17β-estradiol had no effect on inhibition of melanogenesis, suggesting that the DPN-mediated suppression of melanin production was not related with estrogen signaling pathway. Immunoblotting analysis showed that DPN down-regulated the expression of microphthalmia-associated transcription factor (MITF), a central transcription factor of melanogenesis and its down-stream genes including tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. Also, DPN attenuated the phosphorylation of protein kinase A (PKA) and cAMP-response element-binding protein (CREB). Additionally, DPN suppressed the melanin synthesis in UVB-irradiated HaCaT conditioned media culture system suggesting that DPN has potential as an anti-melanogenic activity in physiological conditions. Collectively, our data show that DPN inhibits melanogenesis via downregulation of PKA/CREB/MITF signaling pathway.

Metabolic Activation of Marijuana Constituents, Cannabinoids, in Relation to Their Toxicity for Human and Its Oxidation Mechanism

  • Ikuo, Yamamoto
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.194-199
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    • 2002
  • Many oxidative metabolites of tetrahydrocannabinols (THCs), active components of marijuana, were pharmacologically active, and 11-hydroxy-THCs, 11-oxo-${\Delta}^8$-THC, 7-oxo-${\Delta}^8$-THC, 8$\beta$, 9$\beta$-epoxyhexahydrocannabinol (EHHC), 9$\alpha$, l0$\alpha$-EHHC and 3'-hydroxy-${\Delta}^9$-THC were more active than THC in pharmacological effects such as catalepsy, hypothermia and barbiturate synergism in mice. Cannabidiol (CBD), another major component, was biotransfomred to two novel metabolites, 6-hydroxymethyl-${\Delta}^9$-THC and 3-pentyl-6, 7, 7a, 8, 9, lla-hexahydro-I, 7-dihydroxy-7, 1O-dimethyldibenzo[b, d]oxepin (PHDO) through 8R, 9-epoxy-CBD and 85, 9-epoxy-CBD, respectively. Both metabolites exhibited some pharmacological effects comparable to d9 - THe. Cannabinol (CBN), the other major component, was mainly metabolized to ll-hydroxy-CBN by hepatic microsomes of animals including humans. The pharmacological effects of the metabolite were higher than those of CBN demonstrating that II-hydroxylation of CBN is metabolic activation pathway of the cannabinoid as is the case in THCs. Tolerance and reciprocal cross-tolerance developed to pharmacological effects d8 - THC and ll-hydroxy-d8-THC , and the magnitude of tolerance development produced by the metabolite was significantly higher than that by d8-THC. The results indicate that ll-hydroxy-d8-THC has an important role not only in the pharmacological effects but also its tolerance development of d8 - THe. THCs and their metabolites competed to the specific binding of CP-55, 940, an agonist of cannabinoid receptor, to synaptic membrane from bovine cerebral cortex. The Ki value of THCs and their metabolites were closely paralleled to their pharmacological effects in mice. A novel cytochrome P450 (cyp2c29) was purified and identified as a major enzyme responsible for the metabolic activation of d8-THC at the II-position in the mouse liver. cDNA of CYP2C29 was cloned from a mouse cDNA library and its sequence was determined. The oxidation mechanism of THC by cyp2c29 was proposed.

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Effects of Cardiovascularly Acting Neuroendocrine Agents on Heart Beatings of Pacific Oyster, Crassostrea gigas (순환기 기능 조절기능을 가진 신경내분비계 작용물질이 참굴의 심장 수축기능에 미치는 영향)

  • Park, Kwan-Ha
    • The Korean Journal of Malacology
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    • v.25 no.1
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    • pp.15-22
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    • 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.

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Interleukin-8 and MCP(Monocyte Chemoattractant Protein)-1 expression by the Human Dental Pulps in cultures stimulated with Substance P (사람치수에서 Interleukin-8과 Monocyte chernoattractant protein-1의 분비에 대한 Substance P의 효과에 관한 연구)

  • Shin, Han-Ju;Park, Sang-Hyuk;Choi, Gi-Woon
    • Restorative Dentistry and Endodontics
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    • v.30 no.3
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    • pp.193-203
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    • 2005
  • The induction of the IL-8 and MCP-1 by the stimulation of Substance P and TNF-${\alpha}$ (IL-8 agonist) and the specificity for SP using Spantide (SP antagonist) in the dental pulp tissues was measured quantitatively. In addition, the secretion of the IL-8 in the human dental pulp tissue 36 hrs after the stimulation of SP was observed after the stimulation of SP qualitatively. According to this study the results were as follows: 1. There was the significant IL-8 induction at 36 h after SP (10$^{-4}$M) stimulation of the pulp tissue comparing with the unstimulated dental pulp tissues (p < 0.05) . IL-8 irnmunostaining was weakly detected along the periphery of the pulp tissue after Mock stimulation and IL-8 immunostaining was detected around the fibroblast in the pulp tissue 36h After SP (10$^{-4}$M) stimulation, 2. The secretion of MCP-1 from the dental pulp tissues comparing with Mock stimulation was induced at 36 hrs after TNF-$\alpha$ (40 ng/ml) stimulation, but no induction with SP(10$^{-4}$M) TNF-${\alpha}$ (40 ng/ml) did not induce the IL-8 secretion from the pulp tissue, weak IL-8 imrnunostaining was detected along the periphery of the pulp tissue 3. Spantide (10$^{-5}$M) inhibited IL-8 induction from the pulp tissues 36 h after SP (10$^{-4}$M) stimulation These results suggest that SP significantly induces IL-8 recruiting neutrophils in localized human dental pulp tissue MCP-1 appears to be less involved in the early establishment of pulpal inflammation in response to irritation such as mechanical insult of dentin. SP may have positive relation with the inflammation of the human dental pulp tissues.

Oviposition Patterns Associated with Prolactin Concentration in Domestic Chicken (Gallus domesticus)

  • David, C.G.;Reddy, I.J.;Khub, Singh
    • Asian-Australasian Journal of Animal Sciences
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    • v.16 no.11
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    • pp.1565-1571
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    • 2003
  • Physiological mechanisms, involved in unusual ovulatory sequences in domestic hen are remaining undefined. One hundred individually caged white leghorn birds were divided into two equal groups viz. control and treatment, and 2-bromo-$\alpha$-ergocryptine, was administered to birds in the treatment group to modulate prolactin (PRL) secretion from anterior pituitary gland. The effect of modulation of PRL concentrations on egg production, sequence length and intersequence pause length were studied by analysis of oviposition records of the birds from 24 to 72 weeks of age. The surviving 48 birds in the control and treatment groups averaged $34.58{\pm}1.7$ and $25.67{\pm}1.15$ sequences of oviposition, with a mean sequence length of $9.92{\pm}0.63$ and ${\pm}1.12$ days respectively. Most of the birds had a single characteristically long sequence during the entire reproductive cycle, which averaged $46.04{\pm}3.09$ days in the control birds and $59.33{\pm}4.44$ days in the treated birds. 2-bromo-$\alpha$-ergocriptine treatments had significantly decreased (p$\leq$0.01) the circulating concentrations of PRL compared to the birds of the control group. This resulted in a significant increase (p$\leq$0.01) in the number of laying days in birds of the treatment group with a concomitant decrease in the intersequence pause length. The decreased PRL levels during prime sequences in birds of the both groups, reveals the negative role of the circulating PRL levels on egg production with concomitant shorter intersequence pause length. Hence, modulation of PRL with dopamine agonist may enhance the reproductive efficiency of hens later in life.

Evidence for Adenosine Triphosphate (ATP) as an Excitatory Neurotransmitter in Guinea-Pig Gastric Antrum

  • Kang, Tong-Mook;Xu, Wenxie;Kim, Sung-Joon;Ahn, Seung-Cheol;Kim, Young-Chul;So, In-Suk;Park, Myoung-Kyu;Uhm, Dae-Yong;Kim, Ki-Whan
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.2
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    • pp.165-174
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    • 1999
  • We explore the question of whether adenosine 5'-triphosphate (ATP) acts as an excitatory neurotransmitter in guinea-pig gastric smooth muscle. In an organ bath system, isometric force of the circular smooth muscle of guinea-pig gastric antrum was measured in the presence of atropine and guanethidine. Under electrical field stimulation (EFS) at high frequencies (>20 Hz), NO-mediated relaxation during EFS was followed by a strong contraction after the cessation of EFS (a 'rebound-contraction'). Exogenous ATP mimicked the rebound-contraction. A known $P_{2Y}-purinoceptor$ antagonist, reactive blue 2 (RB-2), blocked the rebound-contraction while selective desensitization of $P_{2Y}-purinoceptor$ with ${\alpha},{\beta}-MeATP$ did not affect it. ATP and 2-MeSATP induced smooth muscle contraction, which was effectively blocked by RB-2 and suramin, a nonselective $P_2-purinoceptor$ antagonist. Particularly, in the presence of RB-2, exogenous ATP and 2-MeSATP inhibited spontaneous phasic contractions, suggesting the existence of different populations of purinoceptors. Both the rebound-contraction and the agonist-induced contraction were not inhibited by indomethacin. The rank orders of agonists' potency were 2-MeSATP > ATP ${ge}$ UTP for contraction and ${\alpha},{\beta}-MeATP\;{\ge}\;{\beta},{\gamma}-MeATP$ for inhibition of the phasic contraction, that accord with the commonly accepted rank order of the classical $P_{2Y}-purinoceptor$ subtypes. Electrical activities of smooth muscles were only slightly influenced by ATP and 2-MeSATP, whereas ${\alpha},{\beta}-MeATP$ attenuated slow waves with membrane hyperpolarization. From the above results, it is suggested that ATP acts as an excitatory neurotransmitter, which mediates the rebound-contraction via $P_{2Y}-purinoceptor$ in guinea-pig gastric antrum.

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The C-terminal Phosphorylation Sites of eel Follicle-Stimulating Hormone Receptor are Important Role in the Signal Transduction

  • Kim, Jeong-Min;Byambaragchaa, Munkhzaya;Kang, Myung-Hwa;Min, Kwan-Sik
    • Development and Reproduction
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    • v.22 no.2
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    • pp.143-153
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    • 2018
  • The large extracellular domain of glycoprotein hormone receptors is a unique feature within the G protein-coupled receptors (GPCRs) family. After interaction with the hormone, the receptor becomes coupled to Gs, which, in turn stimulates adenylyl cyclase and the production of cAMP. Potential phosphorylation sites exist in the C-terminal region of GPCRs. The experiments described herein represent attempts to determine the functions of the eel follicle-stimulating hormone receptor (eelFSHR). We constructed a mutant of eelFSHR, in which the C-terminal cytoplasmic tail was truncated at residue 614 (eelFSHR-t614). The eelFSHR-t614 lacked all potential phosphorylation sites present in the C-terminal region of eelFSHR. In order to obtain the eelFSHR ligand, we produced recombinant follicle-stimulating hormone ($rec-eelFSH{\beta}/{\alpha}$) in the CHO-suspension cells. The expression level was 2-3 times higher than that of the transient expression of eelFSH in attached CHO-K1 cells. The molecular weight of the $rec-eelFSH{\beta}/{\alpha}$ protein was identified to be approximately 34 kDa. The cells expressing eelFSHR-t614 showed an increase in agonist-induced cAMP responsiveness. The maximal cAMP responses of cells expressing eelFSHR-t614 were lower than those of cells expressing eelFSHR-wild type (eelFSHR-WT). The $EC_{50}$ following C-terminal deletion in CHO-K1 cells was approximately 60.4% of that of eelFSHR-WT. The maximal response in eelFSHR-t614 cells was also drastically lower than that of eelFSHR-WT. We also found similar results in PathHunter Parental cells expressing ${\beta}$-arrestin. Thus, these data provide evidence that the truncation of the C-terminal cytoplasmic tail phosphorylation sites in the eelFSHR greatly decreased cAMP responsiveness and maximal response in both CHO-K1 cells and Path-Hunter Parental cells expressing ${\beta}$-arrestin.

Amylase Release from Pancreatic Slices of Rat Treated with Adrenergic Drugs (아드레나린성 약물 전처치 흰쥐의 취절편 효소분비에 관한 실험)

  • Kim, Kyung-Hwan;Kim, Hea-Young;Ahn, Young-Soo;Lee, Woo-Choo;Hong, Sa-Suk
    • The Korean Journal of Pharmacology
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    • v.20 no.2
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    • pp.49-57
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    • 1984
  • The exocrine pancreatic secretion is controlled mainly by gastrointestinal hormones as well as cholinergic nerves. The adrenergic influence on exocrine pancreas is thought not to he important and the evidences supporting this contention are still contradictory. In an effort to elucidate the adrenergic influence on the exocrine pancreas, we have determined the amylase release from pancreatic slices of rats treated with adrenergic drugs. The albino rats of either sex, weighing $60{\sim}80\;g$, were decapitated and the uncinate pancreata were isolated and incubated in screw top vials containing 2 ml krebs-Ringer bicarbonate buffer solution gassed with 95% $O_2$ and 5% $CO_2$. These vials were shaken continuously in a waterbath maintained at $37^{circ}C$, and enzyme release was stimulated with acetylcholine$(10^{-5}M)$. For chronic treatment methoxamine$(an\;{\alpha}-adrenergic\;agonist,\;5\;mg/kg)$, isoproterenol (a\;{\beta}-adrenergic\;agonist,\;10\;mg/kg) and reserpine (0.5 mg/kg) along with cholecystokinin octapeptide$(CCK-op,\;2{\mu}g/kg)$ were given i.p. in rats daily for 3, 5, 7, 9 or 12 days. For acute experiment these drugs were added directly to the incubation medium in a concentration of $10^{-5}M$ except CCK-OP $(10^{-9}M)$. The results are summarized as follows. 1) The addition of methoxamine, isoproterenol or reserpine to the incubation medium containing pancreatic slices augmented the release of amylase induced by acetylcholine and among them the effect of isoproterenol was most prominent. 2) Chronic treatment of methoxamine or reserpine caused enhancement of acetylcholine response in amylase release from pancreatic slice throughout the experimental period, but the amylase release was less than that of control by 12 days isoproterenol treatment. 3) In the pancreatic slices obtained from 12 days treatment of CCK-OP, the amylae release responding to acetylcholine was enhanced. By these finding it is suggested that methoxamine, isoproterenol and reserpine had marked influence on the exocrine pancreatic functions in rats and that these effects are due to their inherent actions rather than sympathetic nerve or adrenergic receptor function.

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Effect of Baclofen on the Cholinergic Nerve Stimulation in Isolated Rat Detrusor (흰쥐의 적출배뇨근에서 baclofen의 콜린성신경 억제작용)

  • Lee, Kwang-Youn;Lee, Keun-Mi;Choi, Eun-Mee;Choi, Hyoung-Chul;Ha, Jeoung-Hee;Kim, Won-Joon
    • Journal of Yeungnam Medical Science
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    • v.12 no.2
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    • pp.246-259
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    • 1995
  • This study aimed to investigate the mechanism of action of baclofen on the detrusor muscle isolated from rat. Rats (Sprague-Dawley) were sacrificed by decapitation and exsanguination. Horizontal muscle strips of $2mm{\times}15mm$ were prepared for isometric myography in isolated muscle chamber bubbled with 95% / 5%-$O_2$ / $CO_2$ at $37^{\circ}C$, and the pH was maintained at 7.4. Detrusor strips contracted responding to the electrical field stimulation (EFS) by 2 Hz, 20 msec, monophasic square wave of 60 VDC. The initial peak of EFS-Induced contraction was tended to be suppresed by ${\alpha},{\beta}$-methylene-adenosine 5'-triphosphate (mATP), a partial agonist of purinergic receptor, and baclofen, a $GABA_B$ receptor agonist (statistically nonsignificant). The late sustained contraction by EFS was suppressed significantly (p < 0.05) by additions of atropione, a cholinergic muscarinic receptor antagonist and baclofen. The adenosine 5'-triphosphate-induced contraction was completely abolished by mA TP but not by baclofen. In the presence of atropine, the subsequent addition of acetylcholine could not contract the muscle strips: but the addition of acetylcholine in the presence of baclofen evoked a contraction to a remarkable extent. These results suggest that in the condition of present study, the cholinergic innervation may play a more important role than the purinergic one, and baclofen suppresses the contractility of rat detrusor by the stimulation of the $GABA_B$ receptors to inhibit the release of neurotransmitter from the cholinergic nerve ending.

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