• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.219-219
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• 1996

Mucin release from hamster tracheal surface epithelial(HTSE) cells can be stimulated by extracellular ATP via activation of P$_2$ purinoceptors located on the cell surface which appears to be coupled to phospholipase C via G proteins. However, our preliminary data indicate that the ATP-induced mucin release involves, in part, activation of PKC, but not an increase in the intracellular Ca++ level, suggesting the presence of another pathway which is separate from the PLC-PKC pathway, In this study, we intended to confirm the previous observation and subsequently identify an additional mechanism. Confluent HTSE cells were metabolically labeled with either $^3$H-glucosamine or $^3$H-arachidonic acid(AA), and release of either $^3$H-mucin or $^3$H-AA was quantified following various treatments. $^3$H-mucin was assayed using the sepharose CL-4B gel-filtration method, whereas $^3$H-AA liberation was measured by counting $^3$H-radioactivity in the chase medium. We found that: (1)Desensitization of PKC by pretreatment with PMA completely abolished the mucin releasing effect of PMA but partially inhibited the ATP-induced mucin release; (2) ATP increases release of $^3$H-AA in a dose-dependent fashion; (3) mepacrine, an inhibitor of PLA$_2$, attenuates ATP-induced mucin release in a dose-dependent fashion. These results confirm our previous notion that the PLC-PKC pathway is responsible, in part, for ATP-induced mucin release. Furthermore, activation of PLA$_2$ appears to be an additional pathway which is involved in ATP-induced mucin release.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.1
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• pp.19-25
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• 1997

The C-terminus ends of the second putative transmembrane domains of both $M_1$ and $M_2$ muscarinic receptors contain a triplet of amino acid residues consisting of leucine (L), tyrosine (Y) and threonine (T). This triplet is repeated as LYT-TYL in $M_1$ receptors at the interface between the second transmembrane domain and the first extracellular loop. Interestingly, however, it is repeated in a transposedfashion (LYT-LYT) in the sequence of $M_2$ receptors. In our previous work, we investigated the possible significance of this unique sequence diversity for determining the distinct differential receptor function at the two receptor subtypes. However, we found mutation of the LYTTYL sequence of $M_1$ receptors to the corresponding $M_2$ receptor LYTLYT sequence demonstrated markedly enhanced the stimulation of phosphoinositide (PI) hydrolysis by carbachol without a change in its coupling to increased cyclic AMP formation. In this work, thus, the enhanced stimulation of PI hydrolysis in the LYTLYT $M_1$ receptor mutant was further investigated. The stimulation of PI hydrolysis by carbachol was enhanced in the mutant $M_1$ receptor, and this change was not due to alterations in the rate of receptor desensitization or sequestration. The observed larger response to carbachol at mutant $M_1$ receptors was also not due to an artifact resulting from selection of CHO cells which express higher levels of G-proteins or phospholipase C. Our data suggest that although the LYTTYL sequence in $M_1$ muscarinic receptors is not involved in determining receptor pharmacology, mutation of the sequence enhanced the coupling of $M_1$ receptors to the stimulation of phospholipase C.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.3
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• pp.277-286
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• 2020

Polycystic kidney disease 2-like-1 (PKD2L1), also known as polycystin-L or TRPP3, is a non-selective cation channel that regulates intracellular calcium concentration. Calmodulin (CaM) is a calcium binding protein, consisting of N-lobe and C-lobe with two calcium binding EF-hands in each lobe. In previous study, we confirmed that CaM is associated with desensitization of PKD2L1 and that CaM N-lobe and PKD2L1 EF-hand specifically are involved. However, the CaM-binding domain (CaMBD) and its inhibitory mechanism of PKD2L1 have not been identified. In order to identify CaM-binding anchor residue of PKD2L1, single mutants of putative CaMBD and EF-hand deletion mutants were generated. The current changes of the mutants were recorded with whole-cell patch clamp. The calmidazolium (CMZ), a calmodulin inhibitor, was used under different concentrations of intracellular. Among the mutants that showed similar or higher basal currents with that of the PKD2L1 wild type, L593A showed little change in current induced by CMZ. Co-expression of L593A with CaM attenuated the inhibitory effect of PKD2L1 by CaM. In the previous study it was inferred that CaM C-lobe inhibits channels by binding to PKD2L1 at 16 nM calcium concentration and CaM N-lobe at 100 nM. Based on the results at 16 nM calcium concentration condition, this study suggests that CaM C-lobe binds to Leu-593, which can be a CaM C-lobe anchor residue, to regulate channel activity. Taken together, our results provide a model for the regulation of PKD2L1 channel activity by CaM.

• Archives of Pharmacal Research
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• v.20 no.1
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• pp.7-12
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• 1997

Glutamate uptake inhibitor, L-trans-pyrrolidine-2, 4-dicarboxylate (PDC, $20{\mu}M$) elevated basal and N-methyl-D-aspartate (NMDA, $100{\mu}M$)-induced extracellular glutamate accumulation, while it did not augment kainate $100{\mu}M$-induced glutamate accumulation in cultured cerebellar granule neurons. However, pretreatment with PDC for 1 h significantly reduced NMDA-induced glutamate accumulation, but did not affect kainate-induced response. Pretreatment with glutamate $(5{\mu}M)$ for 1 h also reduced NMDA-induced glutamate accumulation, but did not kainate-induced response. Upon a brief application (3-10 min), PDC did neither induce elevation of intracellular calcium concentration $([Ca^{2+}]_i)$ nor modulate NMDA-indLiced $[Ca^{2+}]_1$ elevation. Pretreatment with PDC for 1 h reduced NMDA-induced $[Ca^{2+}]_1$ elevation, but it did not reduce kainate-induced $[Ca^{2+}]_1$ elevation. These results suggest that glutamate concentration in synaptic clefts of neurana cells is increased by prolonged exposure (1 h) of the cells to PDC, and the accumulated glutamate subsequently induces selective desensitization of NMDA receptor.

• Research in Community and Public Health Nursing
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• v.8 no.2
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• pp.178-196
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• 1997

The purpose of this study is to identify the kind, the frequency, and the type of Stress Management Program(SMPs) throughout life-span used foreign, recent research. The period of this study was from July 1 to Dec. 10, 1997. The data were collected through Medline using two concepts: stress management programs and life-span. The number of these research were 106 and thirty-one experimental researches that were tested the effectiveness of SMPs throughout life span were selected. The data were analysed by the kind, frequency, and life-span. The results were as follows: 1. The kind and frequency of SMP : The total number of the kind of SMP were twenty-two. The most used SMP was relaxation therapy, 22 out of 31. The second biofeedback was 10, the third, cognitive behavior program was 9, the fourth, nutrition and diet, and education were 7. The others were coping skill(4), cognitive therapy(4), breathing(4), imagery(3), autogenic training(3), sleep and rest(2), meditation(2), information(2), desensitization(2), hypnosis(2), behavior therapy(1), time management (1), visualization(I), yoga(I), diversion(1), and problem solving skill. 2. Throughout life-span: Most SMPs were applied to adolescents, young adults, and middle-adults. Other subjects could not be found under the schooler. 3. The type of SMPs : 28(90.3%) out of 31 research used combined-SMP : two-combined SMP, 5: three-combined SMP, twelve: four-combined SMP, seven: five-combined SMP. 4. Afterward, further study such as meta-analysis are needed in order to identify effective ness of the SMPs.

• Korean Journal of Biological Psychiatry
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• v.19 no.1
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• pp.1-8
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• 2012

The mechanism of psychotherapy is explained by the recent developments in neuroscience and neuroimaging. The purpose of this study is to understand the nature of psychotherapy and to discuss the future of psychotherapy improvement with the help of advances of the neurobiological findings in psychotherapy. For this study, we investigated a wide range of materials. We searched for various researches on psychotherapy, brain, and neurobiology. In addition to the conventional psychodynamic psychotherapy, we investigated research findings on cognitive behavioral therapy, interpersonal psychotherapy and eye movement desensitization and reprocessing (EMDR). Moreover, based on the actual experiences of treating patients, we speculated the neurobiological mechanisms of the process and results of psychotherapy. With the development of neuroscience, we are now able to understand the personal consciousness, unconsciousness and developmental process. Also subdividing the disease is made possible. Personalized treatment has become available, and we are able to predict the prognosis of patients. Our memories are composed by implicit memory and explicit memory. By psychotherapy, we can consciously remember explicit memory, and it becomes easier to explore implicit memory through free association. Through psychotherapy, we will also be able to learn the effect of acquired environment and experience. Psychotherapy is able to correct human behaviors by modifying the memories. Through the regulation of emotions, it becomes possible to modify the memories and correct the behaviors. In this process, doctor-patient relationship is the main factor which cause positive treatment effects. Furthermore imagination therapy or unconscious, non-verbal stimuli could bring about positive treatment effects. Now psychotherapy could be explained and studied by neuroscientific researches. In this sense, we could provide the direction of future advances in neuroscience by the neurobiological understanding of psychotherapy.

• BMB Reports
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• v.32 no.1
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• pp.20-24
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• 1999

The first step of the branch pathway in tryptophan biosynthesis is catalyzed by anthranilate synthase, which is subjected to feedback inhibition by the end product of the pathway. The $trpE^{FBR}$ gene from a mutant Escherichia coli strain coding for anthranilate synthase that was insensitive to feedback inhibition by tryptophan has been cloned. To identify the amino acid changes involved in the feedback regulation of anthranilate synthase, the nucleotide sequence of the mutant $trpE^{FBR}$ gene was determined. Sequence analysis of the $trpE^{FBR}$ gene revealed that four bases were changed in the structural gene while alteration was not found in the 5' control region. Among these base changes, only two base substitutions caused the alterations in amino acid sequences. From the results of restriction fragment exchange mapping, the 61st nucleotide, C to A substitution, that changed $Pro^{21}{\rightarrow}Ser$ was identified as the cause of the desensitization to feedback inhibition by tryptophan. Additional feedback-resistant enzymes of the E. coli anthranilate synthases were constructed by site-directed mutagenesis to examine the effect of the $Ser^{40}\;{\rightarrow}\;Arg^{40}$ change found in the $trpE^{FBR}$ gene of Brevibacterium lactofermentum. From the feedback inhibition analysis, the $Pro^{21}{\rightarrow}Ser$ and $Ser^{40}{\rightarrow}Arg$ mutants maintained about 50% and 90% of their maximal activities, respectively, even at the extreme concentration of 10 mM tryptophan. From these results, we suggest that the $Pro^{21}$ and $Ser^{40}$ residues are involved in the tryptophan binding in the E. coli enzyme.

• Journal of the Korean Chemical Society
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• v.28 no.4
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• pp.251-258
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• 1984

The mechanism of photosensitization and the affect of binder on dye-sensitized ZnO have been studied by surface photovoltage spectroscopy. It has been found that the value of energy trapping level $E_{t1}$ on ZnO is 1.12eV (${\lambda$ = 1,100nm) and that of energy trapping level $E_{t2}$ on dye-sensitized ZnO is 0.99eV (${\lambda$ = 1,250nm) which is shifted towards a longer wavelength. The effect of binder on ZnO has been increased the efficiency of surface photovoltage, but it does not effect the values of energy trapping level. The acid-type dyes agree well with the prediction based on an electron transfer mechanism. The desensitization of the Na salt-type dyes for the intrinsic photoresponse of zinc oxide can be explained by energy transfer mechanism. It has been obtained that the dye-sensitized ZnO indicates the possibility of electrophotographic photosensitizer for the infrared range of light.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1982.05a
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• pp.16.3-17
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• 1982

Nasal polyps were apparently common in many parts of the world and treated for nearly three thousand years. Nasal polyps are round, smooth, soft, semi-translucent, yellow or pale glistening structures, usually attached to the nasal or sinus mucosa by a relatively narrow stalk or pedicle. The incidence of nasal polyps is increased in patients with atopic diseases; it varies from 15% to 25% and now increased using allergy therapy for nasal polyposis treatment. Sinusitis is an inflammation of the mucous membranes of the sinuses. Many agents can cause an inflammatory response, including organisms such as bacteria and viruses, physical and chemical trauma, and antigen antibody reactions. The role of antigen antibody interactions (allergy) in simusitis is not completely understood ; however, patients with allergic rhinitis and nasal polyps have a high incidence of sinusitis. Recently authors have experienced two cured cases of nasal polyposis combined with chronic sinusitis by allergy therapy, that cases were treated only allergy thereapy after Caldwell Luc operation with ethmoidectomy and polypectomy. At now cases were not recur of nasal polyps and nasal symptoms. So the cases were reported with a brief review of literature.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.585-595
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• 2018

Amitriptyline, a tricyclic antidepressant, is commonly used to treat depression and neuropathic pain, but its mechanism is still unclear. We tested the effect of amitriptyline on 5-hydroxytryptamine 3 ($5-HT_3$) receptor currents and studied its blocking mechanism because the clinical applications of amitriptyline overlapped with $5-HT_3$ receptor therapeutic potentials. Using a whole-cell voltage clamp method, we recorded the currents of the $5-HT_3$ receptor when 5-HT was applied alone or co-applied with amitriptyline in cultured NCB-20 neuroblastoma cells known to express $5-HT_3$ receptors. To elucidate the mechanism of amitriptyline, we simulated the $5-HT_3$ receptor currents using Berkeley $Madonna^{(R)}$ software and calculated the rate constants of the agonist binding and receptor transition steps. The $5-HT_3$ receptor currents were inhibited by amitriptyline in a concentration-dependent, voltage-independent manner, and a competitive mode. Amitriptyline accelerated the desensitization of the $5-HT_3$ receptor. When amitriptyline was applied before 5-HT treatment, the currents rose slowly until the end of 5-HT treatment. When amitriptyline was co-applied with 5-HT, currents rose and decayed rapidly. Peak current amplitudes were decreased in both applications. All macroscopic currents recorded in whole cell voltage clamping experiments were reproduced by simulation and the changes of rate constants by amitriptyline were correlated with macroscopic current recording data. These results suggest that amitriptyline blocks the $5-HT_3$ receptor by close and open state blocking mechanisms, in a competitive manner. We could expand an understanding of pharmacological mechanisms of amitriptyline related to the modulation of a $5-HT_3$ receptor, a potential target of neurologic and psychiatric diseases through this study.