• 대한약리학회지
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• 제5권2호
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• pp.115-119
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• 1969

The authors studied the adrenotropic receptors of isolated urinary bladder from Sebastes inermis, using adrenergic activators such as epinephrine, nor-epinephrine, isoproterenol and phenylephrine and adrenergic blocking agents such as phenoxybenzamine, pronethalol and propranolol. The studies have revealed the following results. 1) The spontaneous motility of isolated bladder from Sebastes inermis was inhibited by epinephrine nor-epinephrine, isoproterenol and phenylephrine. 2) The inhibitory effect of phenylephrine on the Sebastes inermis bladder was blocked by phenoxybensamine. 3) The inhibitory effect of isoproterenol was blocked by pronethalol and propranolol. 4) The effect of epinephrine and nor-epinephrine on the Sebastes inermis bladder was usually not blocked by either kind of blocking agent alone, but was blocked by a combination of ${\alpha}\;and\;{\beta}$ blockades. 5) It is, therefore, concluded that the Sebastes inermis bladder has alpha and that both receptors, and that both receptors subserve retaxation or inhibition.

• Biomolecules & Therapeutics
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• 제6권3호
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• pp.276-282
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• 1998

Retinoids regulate a wide variety of biological processes such as cellular proliferation and differentiation in many cell types. They have also shown to stimulate replication of several viruses including human cytomegalovirus (CMV). Retinoid signalling pathway involves two distinct subfamilies of nuclear receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs) that bind to specific retinoic acid response elements (RAREs) in the promoter regions of retinoid-target genes. Here, we characterized RAREs in the regulatory regions of the CMV and of the hepatitis B vi.us (HBV). The viral RAREs, i.e., CMV-RARE and HBV-RARE, are composed of two consensus RARE half-sites (A/GGGTCA) arranged as a direct repeat separated by 5-bp and 1-bp, respectively. The RAREs were activated by both RAR/RXR heterodimers and RXR homodimers in transient transfection experiments. We also found that COUP-TF$\alpha$ (chicken ovalbumin upstream promoter-transcription factor u) and COUP-TF$\beta$ repressed the retinoid response of the viral elements. Further we demonstrated that previously known retinoid antagonist, SRI 1330, repressed retinoid-induced transactivation of the CMV-RARE. These results implicate Vitamin A, it's nuclear receptors and COUP-TFs as important regulators of the CMV and HBV pathogenesis and the SRl1330 as potential negative modulator of such retinoid-dependent processes.

• The Korean Journal of Physiology and Pharmacology
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• 제3권5호
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• pp.461-469
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• 1999

Glutamate and ${\gamma}-aminobutyric$ acid (GABA) are major excitatory and inhibitory neurotransmitters in the vertebrate retina, respectively. Using the whole-cell patch clamp technique and a rapid solution changer, glutamate and GABA receptors have been extensively investigated in carp retina. Glutamate receptors on both horizontal and amacrine cells may be an AMPA preferring subtype, which predominantly consists of flop splice variants. $GABA_A$ and $GABA_C$ receptors coexist in bipolar cells and they both show significant desensitization. Kinetics analysis demonstrated that activation, deactivation and desensitization of the $GABA_C$ receptor-mediated response of these cells are overall slower than those of the $GABA_A$ response. Endogenous modulator $Zn^{2+}$ in the retina was found to differentially modulate the kinetic characteristics of the $GABA_C$ and $GABA_A$ responses.

• The Korean Journal of Physiology and Pharmacology
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• 제7권1호
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• pp.1-3
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• 2003

To investigate the receptors mediating the regulation of norepinephrine (NE) release in human cerebral cortex slices, we examined the effects of opioid agonists for ${\mu}$-, ${\delta}$-, and ${\kappa}$-receptors on the high potassium (15 mM)-evoked release of [$^3H$]NE. [$^3H$]NE release induced by high potassium was calcium-dependent and tetrodotoxin-sensitive. [$D-Pen^2$, $D-Pen^5$]enkephalin (DPDPE) and deltorphin II (Delt II) inhibited the stimulated release of norepinephrine in a dose-dependent manner. However, Tyr-D-Ala-Gly-(Me)Phe-Gly-ol and U69,593 did not influence the NE release. Inhibitory effect of DPDPE and Delt-II was antagonized by naloxone, naltrindole, 7-benzylidenaltrexone and naltriben. These results suggest that both ${\delta}_1$ and ${\delta}_2$ receptors are involved in regulation of NE release in human cerebral cortex.

• The Korean Journal of Physiology and Pharmacology
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• 제11권5호
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• pp.221-226
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• 2007

Melittin-induced tonic pain model is characterized by local inflammation, edema, spontaneous flinchings, and sustained mechanical hypersensitivity. These nociceptive responses are mediated through selective activation of capsaicin-sensitive primary afferent fibers by melittin. The present study was undertaken to elucidate the role of peripheral 5-hydroxytryptamine(5-HT) receptors in the melittin-induced nociceptive responses. Changes in mechanical threshold, flinching behaviors and paw thickness were measured in rat intraplantarly injected with melittin($40{\mu}g/paw$) alone or treated together with melittin and 5-HT receptor antagonists. WAY-100635($100{\mu}g\;&\;200{\mu}g/paw$), isamoltane hemifumarate($100{\mu}g\;&\;200{\mu}g/paw$), methysergide maleate($60{\mu}g,\;120{\mu}g\;&\;200{\mu}g/paw$) and ICS-205,930($100{\mu}g\;&\;200{\mu}g/paw$) were intraplantarly injected 20 min before melittin injection. All 5-HT receptor antagonists tested in this experiment significantly attenuated the ability of melittin to reduce mechanical threshold and to induce flinching behaviors. 5-HT receptor antagonists, except ICS-205,930, had mild inhibitory effect on melittin-induced edema. These experimental findings suggest that multiple peripheral 5-HT receptors are involved in the melittin-induced nociceptive responses.

• Animal cells and systems
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• 제2권2호
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• pp.153-164
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• 1998

Cytokines regulate proliferation, differentiation and functions of haemotopoietic cells. Each cytokine possesses a variety of activities on various target cells (pleiotropy) and various cytokines have similar and overlapping activities on the same target cells (redundancy). The nature of these cytokine activities predicts unique feature of cytokine receptors, namely, cytokine has multiple receptors, different cytokines share a common receptor, and different cytokine receptors are linked to common signaling pathways. cDNA cloning of genes for cytokine receptors revealed distinct sets of receptor family with different structural features. The cytokine receptor superfamily consists of a largest family, and contains more than twenty cytokine receptor subunits. This receptor has common structural features in both extracellular and intracellular regions without tyrosine kinase domain. Another striking feature of the receptor is to share common subunit of multiple cytokines, which partly explains the redundancy of activities of some cytokines. Recent studies revealed detailed signaling events of the cytokine receptor, the primary activation of JAK and subsequent phosphorylation of tyrosine residues of receptor, and various cellular proteins. Many SH2 containing adapter proteins play an important role in cytokine signals, and this system has similarities with tyrosine kinase receptor signal transduction. STAT may mainly account for cytokine specific functions as suggested by knockout mice studies. It is of importance to note that cytokine activates multiple signaling pathways and the balance and combination of related signaling events may determine the specificity of functions of cytokines.

• 대한약리학회지
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• 제3권1호
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• pp.43-49
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• 1967

Supplemental studies were made on the adrenotropic receptors of the rat uterus, using adrenergic activators such as phenylephrine, norepinephrine, epinephrine, and isoproterenol and adrenergic blocking agents such as phenoxybenzamine and inderal. The studies have revealed the following results : 1. Phenylephrine, norepinephrine, epinephrine, and isoproterenol inhibited the spontaneous motility of the isolated rat uterus in the following order : Isoproterenol>epinephrine>norepinephrine>phenylephrine. 2. The inhibitory responses of the isolated rat uterus to phenylephrine and epinephrine were abolished by the pretreatment with phenoxybenzamine. 3. The inhibitory responses of the isolated rat uterus to isoproterenol and epinephrine were not affected by phenoxybenzamine. 4. The motility of the isolated rat uterus pretreated with inderal was stimulated by phenylephrine, norepinephrine and epinephrine. 5. The inhibitory responses of the isolated rat uterus to isoproterenol were abolished by the pretreatment with inderal. 6. The motility of the isolated rat uterus pretreated with inderal and phenoxybenzamine was not affected by phenylephrine, norepinephrine and epinephrine. 7. It is, therefore, concluded that the rat uterus has both alpha excitatory and beta inhibitory receptors, with beta inhibitory receptors predominating.

• 통합자연과학논문집
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• 제5권1호
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• pp.22-26
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• 2012

Chemokine receptor antagonists have potential applications in field of drug discovery. Although the chemokine receptors are G-protein-coupled receptors, their cognate ligands are small proteins (8 to 12 kDa), and so inhibiting the ligand/receptor interaction has been challenging. In particular, CCR2 and CCR5 and their ligands have been implicated in the pathophysiology of a number of diseases, including rheumatoid arthritis and multiple sclerosis. Based on their roles in disease, they have been attractive targets for the pharmaceutical industry, targeting both CCR2 and CCR5 could be a useful strategy. Because of the importance of these receptors, providing information regarding the binding site is of prime importance. Herein, we report the comparison of CCR2 of CCR5 binding sites both sequentially as well as structurally. We also urged the importance of crucial residues in the binding site, to facilitate the development of dual antagonists targeting both the receptors. These results could also be useful for the design of novel and potent dual CCR2 and CCR5 antagonists using structure based drug design.

• Molecules and Cells
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• 제42권1호
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• pp.1-7
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• 2019

Macrophage is an important innate immune cell that not only initiates inflammatory responses, but also functions in tissue repair and anti-inflammatory responses. Regulating macrophage activity is thus critical to maintain immune homeostasis. Tyro3, Axl, and Mer are integral membrane proteins that constitute TAM family of receptor tyrosine kinases (RTKs). Growing evidence indicates that TAM family receptors play an important role in anti-inflammatory responses through modulating the function of macrophages. First, macrophages can recognize apoptotic bodies through interaction between TAM family receptors expressed on macrophages and their ligands attached to apoptotic bodies. Without TAM signaling, macrophages cannot clear up apoptotic cells, leading to broad inflammation due to over-activation of immune cells. Second, TAM signaling can prevent chronic activation of macrophages by attenuating inflammatory pathways through particular pattern recognition receptors and cytokine receptors. Third, TAM signaling can induce autophagy which is an important mechanism to inhibit NLRP3 inflammasome activation in macrophages. Fourth, TAM signaling can inhibit polarization of M1 macrophages. In this review, we will focus on mechanisms involved in how TAM family of RTKs can modulate function of macrophage associated with anti-inflammatory responses described above. We will also discuss several human diseases related to TAM signaling and potential therapeutic strategies of targeting TAM signaling.

• 한국동물생명공학회지
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• 제36권4호
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• pp.169-174
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• 2021

Mutations in the luteinizing hormone/chorionic gonadotropin receptors (LH/CGRs), representatives of the G protein-coupled receptor family, have been rapidly identified over the last 20 years. This review aims to compare and analyze the data reported the activating and inactivating mutations of the LH/CGRs between human, rat, equine and fish, specifically (Japanese eel Anguilla japonica). Insights obtained through detailed study of these naturally-occurring mutations provide a further update of structure-function relationship of these receptors. Specifically, we present a variety of data on eel LH/CGR. These results provide important information about LH/CGR function in fish and the regulation of mutations of the highly conserved amino acids in glycoprotein hormone receptors.