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1.
Acta Pharmaceutica Sinica ; (12): 2453-2460, 2022.
Article in Chinese | WPRIM | ID: wpr-937058

ABSTRACT

Wuzhi tablet (WZ) is a prescribed herbal medicine extracted from Schisandra sphenanthera, which is widely used to protect the liver injury and drug-induced hepatotoxicity in clinical practices. Previous studies showed that WZ significantly increased the blood concentrations of tacrolimus, cyclosporine A, paclitaxel by inhibiting the cytochrome P450 3A (CYP3A)-mediated metabolism. CYP3A4 and CYP3A5 are the most important isoenzymes among the CYP3A subfamily. However, there are some differences in the catalytic and inhibitory activities between CYP3A4 and CYP3A5, which may lead to different risk of drug-drug and herb-drug interactions, and the risks may be further amplified in vivo. Currently, few reports have compared the herbal medicine inhibitory effects between CYP3A4 and CYP3A5 mediated metabolic reactions. Therefore, detailing the inhibitory effect of WZ on CYP3A4 and CYP3A5 will help understand and predict the potential herb-drug interaction. The results showed that WZ inhibited CYP3A4 and CYP3A5 in a NADPH-, time- and concentration- dependent manner. WZ showed more potent inhibition on CYP3A5 than CYP3A4. Cautions warranted when combining WZ with other therapeutic drugs to avoid the potential herb-drug interaction.

2.
Article in Chinese | WPRIM | ID: wpr-906474

ABSTRACT

Oral nanoparticles (NPs) has gradually become a approach to improve oral bioavailability of biopharmaceutics classification system (BCS) Ⅱ, Ⅲ, Ⅳ drugs, and the transmembrane transport mechanism in the gastrointestinal tract largely depends on physicochemical characteristics of NPs. It would be beneficial to design the NPs with high transport efficiency and effectively improve the oral bioavailability of drugs by adopting a reasonable research model to analyze the transmembrane mechanism of the oral NPs and exactly reveal the relationship between the physicochemical properties and the transport mechanism of NPs. This review focused on summarizing the transmembrane approaches of oral NPs, comparing the advantages and disadvantages of the common cell models, concluding the potential interaction between the physicochemical properties and transmembrane process of NPs, and proposing the research strategy of transport mechanism based on in situ intestinal perfusion, with the purpose of discovering a suitable research model for studying the transport mechanism of different NPs, providing a basis for regulating the transport performance of the NPs to improve the oral bioavailability, and expanding the application of oral NPs in the development of new drugs.

3.
Article in Chinese | WPRIM | ID: wpr-880035

ABSTRACT

METHODS@#From January 2005 to December 2013, 83 patients with refractory/recurrent CD20@*RESULTS@#All the patient achieved complete response. The median follow.up time was 39 months. Both the two groups collected peripheral blood stem cells successfully, and had no difference in hematopoietic reconstitution time. Three patients in treatment group and six patients in control group relapsed and the three year overall survival and EFS in treatment group was significantly higher than that in control group, that is(93.0% vs 73.1%, P=0.037) and (89.5% vs 65.4%, P=0.034), respectively. Subgroup analysis showed that: compared with the treatment group in which using R in the whole courses(before and after transplantation, and collection of stem cells) was superior to the control group in both OS and EFS, with the OS 97% vs 87.5% (P>0.05) and EFS 97% vs 76.2% (P=0.05) respectively. While stratified by the different courses of rituximab, the OS was 88.9% (1-2 courses, 9 cases), 93.1% (3-4 courses, 29 cases), 94.7%(more than 5 courses,19 cases), and EFS was 77.8%, 89.7% and 94.7%, respectively.@*CONCLUSION@#For the patients with refractory/recurrent CD20


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Disease-Free Survival , Hematopoietic Stem Cell Transplantation , Hodgkin Disease , Humans , Lymphoma, Non-Hodgkin/drug therapy , Rituximab/therapeutic use , Transplantation, Autologous , Treatment Outcome
4.
Article in Chinese | WPRIM | ID: wpr-879034

ABSTRACT

Kudzu plants in the subfamily sphenoideae of Leguminosae are commonly used herbs in China, Japan, Korea, India and Thailand, with a long history of medicinal use. They are recorded in Chinese Pharmacopoeia, Japanese Pharmacopeia, Korea Pharmacopeia, Ayurveda Pharmacopoeia of India and Flora of Thailand. There are 15-20 species of Pueraria in the world, including 7 species and 2 varieties in China. At present, there are 6 species with medicinal value, such as Pueraria lobata and P. thomsonii. The main chemical components of the genus are isoflavones, flavonoids, terpenes, steroids, coumarins, puerarin glycosides and benzopyrans. A total of 240 compounds have been isolated and identified from this genus, and their pharmacological effects mainly include improvement of the cardiovascular system, antioxidant, hypoglycemic, antipyretic, anti-inflammatory, anti-alcoholic and estrogen-like effects. In this study, chemical constituents and pharmacological activities of Pueraria at home and abroad were systematically summarized, in order to provide references for the material basis, quality control and further development of Pueraria genus.


Subject(s)
China , Isoflavones/pharmacology , Japan , Plant Roots , Pueraria , Republic of Korea , Thailand
5.
Article in Chinese | WPRIM | ID: wpr-846443

ABSTRACT

Objective: To investigate the mechanism of sovereign medicines in Sanren Decoction on coronavirus disease 2019 (COVID-19) through network pharmacology and molecular docking methods. Methods: The main active ingredients of sovereign medicines in Sanren Decoction (Armeniacae Semen Amarum, Amomun kravanh Pierre ex Gagnep, and Coicis Semen) were obtained and screened from by TCMSP and TCMID V2.0, combined with related research. Using UniPort database to query the target proteins corresponding to the active ingredients, then a component-target network was constructed by Cytoscape 3.7.2. PPI network was constructed through the STRING website, and cytoHubba was used to analysis the key subnetworks. CTD database was used to analyze GO and KEGG enrichment of the active ingredient target proteins of Sanren Decoction. Using the active ingredients of sovereign medicines in Sanren Decoction and related chemical drugs such as lopinavir as ligands, molecular docking with the SARS-CoV-2 3CL hydrolase was performed through the CB-Dock website. Results: Sovereign medicines in Sanren Decoction had 39 active ingredients, corresponding to 168 target proteins. The GO enrichment analysis obtained 25 biological processes (BP) items, 14 related items of cell composition (CC), and two molecular function (MF) item, respectively. KEGG enrichment screened 36 signaling pathways such as innate immune system, cytokine signaling in immune system, signaling by interleukins. The molecular docking results suggested that the active ingredients of mairin, ziziphin_qt, and oleanolic acid of sovereign medicines in Sanren Decoction had good binding energy with SARS-CoV-2 3CL hydrolase, and the Vina score of them were similar to those of lopinavir (the 3CLpro inhibitor) and remdesivir (RNA-dependent RNA polymerase inhibitor). Conclusion: Sovereign medicines in Sanren Decoction may participate in inflammation-related signaling pathways by regulating inflammatory factors, regulating multiple physiological processes of the disease with multi-components, multi-targets, and multi-pathways. It plays a certain intervention role in the treatment of COVID-19 and its active ingredients have potential resistance to SARS-CoV-2.

6.
Article in Chinese | WPRIM | ID: wpr-818366

ABSTRACT

Objective Trihostatin A (TSA) is a histone deacetylase inhibitor of oxime salts, which has certain anti-tumor activity. This article mainly investigates the molecular mechanism of TSA inhibiting cell proliferation through p-AKT/p-mTOR pathway in gastric cancer cells. Methods Gastric cancer cell line-SGC-7901 were treated with TSA of different concentrations, and the inhibition rate of TSA on the cells was detected by MTT assay. The cells were divided into control group (without any treatment), TSA-treated group (200ng/ml TSA), p-AKT covering group (200 ng/mL TSA+8 μg/mL SC79) and autophagy inhibition group (5 mmol/mL 3-methyladenine+200 ng/mL TSA). The protein expression distribution of Lc3 in control and TSA group were detected by cell immunofluorescence staining. The relative expression levels of p-AKT, p-mTOR and autophagy related proteins Lc3 and P62 in control group, TSA group and p-AKT covering group were detected by Western blot. The proliferation of cells in control group, TSA group, p-AKT covering group and autophagy inhibition group were measured by EdU and cell count assay. Results After 24h of treatment, Lc3 in TSA group formed a large number of granular aggregates in the cytoplasm, and the fluorescence distribution changed from the initial diffuse to dense. The TSA group showed a significant reduction in green fluorescence compared with the control group in the EdU experiment. The expression levels of p-AKT in the control group, TSA group and the autophagy inhibition group were 1.78±0.19, 0.92±0.03 and 1.71±0.19, respectively, and Lc3 were 0.21±0.01, 0.79±0.06 and 0.55±0.10, respectively. Compared with the control group, the relative expression level of p-AKT in the TSA group all decreased, while the expression level of Lc3 increased (P <0.05). p-mTOR in the three groups was 0.80±0.16, 0.45±0.04 and 0.98±0.16, respectively. Compared with the control group, the relative expression level of p-mTOR in the TSA group all decreased (P <0.05). P62 in the three groups was 1.17±0.15, 0.48±0.08 and 0.77±0.10, respectively. Compared with the control group, the relative expression level of P62 in the TSA group all decreased (P<0.05). Compared with the TSA group, p-AKT, p-mTOR and P62 expression in the p-AKT covering group increased (P<0.05), while Lc3 expression decreased (P<0.05). Compared with the control group, the inhibition effect of cell growth curve was the most obvious in the TSA group, while the cell growth curve of p-AKT covering group and autophagy inhibition group showed a partial recovery compared with the TSA group. Conclusion TSA can promote autophagy by inhibiting p-AKt/p-mTOR pathway, thus inhibiting the proliferation of gastric cancer cells.

7.
Acta Pharmaceutica Sinica ; (12): 765-770, 2018.
Article in Chinese | WPRIM | ID: wpr-779934

ABSTRACT

The study was designed to investigate the effect of IMPDH1 gene polymorphism on the pharmacodynamics of mycophenolic acid in the renal transplant patients. 315 patients with renal transplantation were treated with triple immunotherapy (mycophenolic acid + tacrolimus + prednisone). The Agena MassARRAY assay was used to detect the IMPDH1 genotypes in patients above. The plasma drug concentration of mycophenolic acid (MPA) and its main metabolite mycophenolic acid glucuronide (MPAG) was detected by high performance liquid chromatography (HPLC). The correlation between IMPDH1 gene polymorphism (rs10954183, rs12536006, rs13242340, rs2278293, rs2288549) and rejection and postoperative infection in renal transplant recipients were analyzed by SPSS 21 software. The result showed that IMPDH1 rs2288549 GG is a risk factor for acute rejection after renal transplantation (PIMPDH1 rs2278293 CT is a risk factor for infection after renal transplantation (PIMPDH1 rs2288549 is an important factor of acute rejection after renal transplantation, IMPDH1 rs2278293 is an important factor affecting the emergence of infection after renal transplantation. The SNPs may help to optimize clinical medication to reduce the incidence of adverse reaction.

8.
International Eye Science ; (12): 1516-1518, 2017.
Article in Chinese | WPRIM | ID: wpr-641254

ABSTRACT

AIM: To evaluate the effect of orthokeratology on progression of juvenile myopia and analysis its influencing factors.METHODS: Totally 97 patients (189 eyes,aging from 8 to 17 years old) who received orthokeratology lenses treatment in our hospital from January 2012 to December 2014,were followed up for 2a.The visual acuity,corneal curvature,diopter,and ocular axial length were observed.Factors of influencing myopia progress in juvenile were analyzed.RESULTS: At 1mo after receiving orthokeratology contact lenses,the visual acuity and corneal curvature were changed compared with that of before(P<0.001).After 2a of receiving orthokeratology contact lenses,the difference was significant compared with baseline: spherical equivalence (-0.51±0.64D,t=10.864,P<0.001),axial length(0.33±0.31mm,t=14.879,P<0.001),corneal astigmatism (-0.25±0.43D,t=5.375,P<0.001).Statistic analysis showed that there was a negative correlation between the spherical equivalence and age,baseline of diopter or ocular axial length(P<0.05).CONCLUSION: Orthokeratology can effectively improve the visual acuity of patients.Although there is slightly progression in diopter and ocular length after 2a of wearing orthokeratology contact lenses.Orthokeratology is an effective treatment on controlling progression of juvenile myopia,especially in the elder children who with the longer basic axial length and the greater diopter.

9.
Acta Pharmaceutica Sinica ; (12): 760-765, 2017.
Article in Chinese | WPRIM | ID: wpr-779655

ABSTRACT

The paper was aimed to investigate the association of VDR polymorphisms with tacrolimus (FK506) concentration in Chinese renal transplant recipients. A total of 114 renal transplant recipients receiving tacrolimus were genotyped for VDR rs1540339 and rs2853559 by Agena Bioscience MassARRAY® system and CYP3A5*3 by PCR-RFLP method. Trough concentrations of tacrolimus on day 7 after renal transplantation were collected from clinical data. Statistical analysis was performed with Spearman's correlation, Mann-Whitney U test and Kruskal-Wallis H test. The dose-adjusted concentration of tacrolimus in VDR rs2853559 GA and GG carriers were considerably higher than that of AA carriers. After stratification by CYP3A5*3 genotypes, VDR rs2853559 GA and GG carriers had a higher dose-adjusted tacrolimus concentration than that in AA carriers in CYP3A5 nonexpresser. CYP3A5*3 and VDR rs2853559 explained 45.6% variability of tacrolimus C0/D. In CYP3A5 non-expressers, VDR rs2853559 explained 14.4% variability of tacrolimus C0/D. The results illustrated that VDR rs2853559 polymorphisms was associated with tacrolimus concentrations, and the determination of this SNP may be useful for individualized medicine of tacrolimus.

10.
Acta Pharmaceutica Sinica ; (12): 80-85, 2016.
Article in Chinese | WPRIM | ID: wpr-320013

ABSTRACT

This study aims to investigate the function of two SNPs (rs8904C > T and rs696G >A) in 3' untranslated region (3'UTR) of NFKBIA gene by constructing luciferase reporter gene. A patient's genomic DNA with rs8904 CC and rs696 GA genotype was used as the PCR template. Full-length 3'UTR of NFKBIA gene was amplified by different primers. After sequencing validation, these fragments were inserted to the luciferase reporter vector, pGL3-promoter to construct recombinant plasmids containing four kinds of haplotypes, pGL3-rs8904C/rs696G, pGL3-rs8904C/rs696A, pGL3-rs8904T/rs696G and pGL3-rs8904T/rs696A. Then these plasmids were transfected into LS174T cells and the luciferase activity was detected. Compared with pGL3-vector transfected cells (negative control), the luciferase activity of the four kinds of recombinant plasmids was significantly decreased (P < 0.001). For rs696G > A, the luciferase activity of the recombinant plasmids containing A allele (pGL3-rs8904C/rs696A and pGL3-rs8904T/rs696A) was about 45.1% (P < 0.05) and 56.1% (P < 0.001) lower than those containing G allele (pGL3-rs8904C/rs696G and pGL3-rs8904T/rs696G), respectively. For rs8904C > T, there were no significant differences in the luciferase activity between the recombinant plasmids containing T allele and those with C allele. Together, the luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR were constructed successfully and rs696G > A could decrease the luciferase activity while rs8904C >T didn't have much effect on the luciferase activity.


Subject(s)
3' Untranslated Regions , Genes, Reporter , Genetic Vectors , Humans , I-kappa B Proteins , Genetics , Luciferases , NF-KappaB Inhibitor alpha , Plasmids , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Transfection
11.
Acta Pharmaceutica Sinica ; (12): 1240-2016.
Article in Chinese | WPRIM | ID: wpr-779302

ABSTRACT

The study aims to investigate the associations of SLCO1B1 polymorphisms with tacrolimus concentrations in Chinese renal transplant recipients. Blood samples and clinical data were collected from 89 renal transplant recipients with tacrolimus treatment. CYP3A5*3 genotypes were detected by PCR-RFLP method and SLCO1B1 (rs2306283, rs4149032) genotypes were detected by Agena Bioscience Mass ARRAY ® system. Trough concentrations of tacrolimus on day 7 after renal transplantation were collected from clinical data. Correlations between genetic polymorphisms and tacrolimus concentrations were analyzed by SPSS. In CYP3A5 nonexpressers, the dose-adjusted concentration of tacrolimus in SLCO1B1 rs2306283 CC carriers was considerably higher than that in CT and TT carriers. The results illustrated that SLCO1B1 rs2306283 polymorphisms were associated with tacrolimus concentrations, and genotyping for this SNP may be usefulfo r individualized medicine of tacrolimus.

12.
Article in Chinese | WPRIM | ID: wpr-779138

ABSTRACT

This study aims to investigate the function of two SNPs (rs8904C > T and rs696G > A) in 3' untranslated region (3'UTR) of NFKBIA gene by constructing luciferase reporter gene. A patient's genomic DNA with rs8904 CC and rs696 GA genotype was used as the PCR template. Full-length 3'UTR of NFKBIA gene was amplified by different primers. After sequencing validation, these fragments were inserted to the luciferase reporter vector, pGL3-promoter to construct recombinant plasmids containing four kinds of haplotypes, pGL3-rs8904C/rs696G, pGL3-rs8904C/rs696A, pGL3-rs8904T/rs696G and pGL3-rs8904T/rs696A. Then these plasmids were transfected into LS174T cells and the luciferase activity was detected. Compared with pGL3- vector transfected cells (negative control), the luciferase activity of the four kinds of recombinant plasmids was significantly decreased (P A, the luciferase activity of the recombinant plasmids containing A allele (pGL3-rs8904C/rs696A and pGL3-rs8904T/rs696A) was about 45.1% (P P T, there were no significant differences in the luciferase activity between the recombinant plasmids containing T allele and those with C allele. Together, the luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR were constructed successfully and rs696G > A could decrease the luciferase activity while rs8904C > T didn't have much effect on the luciferase activity.

13.
Acta Pharmaceutica Sinica ; (12): 180-184, 2015.
Article in Chinese | WPRIM | ID: wpr-251798

ABSTRACT

The study aims to investigate the associations of SUMO4 polymorphisms with tacrolimus concentrations in Chinese renal transplant recipients. Blood samples and clinical data were collected from 132 renal transplant recipients with tacrolimus treatment. CYP3A5*3 genotypes were detected by PCR-RFLP, and SUMO4 (rs237024, rs237025) genotypes were detected by Sequenom® MassARRAY system. SUMO4 rs237024 and rs237025 genotypes were in complete linkage disequilibrium (D' = 1). The dose-adjusted concentration of tacrolimus in SUMO4 rs237024A-rs237025A (GA-GA +AA-AA) carriers was considerably higher than that in GG-GG carriers (P < 0.05). After stratification by CYP3A5*3 genotypes, SUMO4 rs237024A-rs237025A carriers (GA-GA+AA-AA) had a higher dose-adjusted tacrolimus concentration than that in GG carriers in CYP3A5 expresser (P < 0.05). The results illustrated that SUMO4 rs237024 and rs237025 polymorphisms were associated with tacrolimus concentrations, and the test of these genotypes may be useful for individualized medicine of tacrolimus.


Subject(s)
Asians , Genetics , Cytochrome P-450 CYP3A , Genetics , Genotype , Humans , Immunosuppressive Agents , Blood , Therapeutic Uses , Kidney , Kidney Transplantation , Linkage Disequilibrium , Polymorphism, Single Nucleotide , Small Ubiquitin-Related Modifier Proteins , Genetics , Tacrolimus , Blood , Therapeutic Uses
14.
International Eye Science ; (12): 662-665, 2015.
Article in Chinese | WPRIM | ID: wpr-637227

ABSTRACT

AIM: To explore the relationship of central retinal vein occlusion ( CRVO) and atherosclerosis ( AS) . METHODS:Fifty cases of CRVO patients were chosen as the observation group in our hospital from October 2012 to October 2014, other 50 patients with AS ( non-CRVO) as control group. In the control group, 22 cases of AS mild stenosis, moderate stenosis in 24 cases, 4 cases of severe stenosis ( 3 cases implanted stent ) . According to the severity, two grade prevention primary prevention therapy, and cerebral vascular disease treating stroke, corresponding drug treatment was undergone. Two groups of patients were performed cervical carotid artery color Doppler ultrasound examination, including assessing plaque, carotid artery intima-media thickness ( IMT) , the degree of stenosis of internal carotid artery blood flow velocity and the systolic peak ( PSV ) , end diastolic blood flow velocity ( EDV) , resistance index ( RI) values for kinetic parameters etc. All the indexes of the two groups were compared with color Doppler ultrasound examination results, to evaluate the correlation between CRVO and AS. RESULTS: In the observation group, 15 cases were detected of carotid artery with mild stenosis, 28 cases of arterial diameter reduced CONCLUSION: CRVO and AS are highly correlated, the neck of Doppler ultrasound examination can clearly reflect the central retinal vein blood supply, the standard treatment for AS disease, can reduce the risk of CRVO, with certain clinical significance.

15.
Article in Chinese | WPRIM | ID: wpr-337913

ABSTRACT

The paper is aimed to search more natural plant antioxidants and further research and develop new medicinal plant resources in Guizhou. The Guizhou special miao medicine "bod zangd dak" was extracted with 60% ethanol. The antioxidant activity of the different polarity components separated from the extract was tested by DPPH method with ascorbic acid as positive control. The results showed that the IC50 of the different polarity components was as following: ascorbic acid (0.033 4 g x L(-1)) < ethyl acetate components (0.052 3 g x L(-1)) < total tannins components (0.054 9 g x L(-1)) < 60% ethanol extraction components (0.076 7 g x L(-1)) < butanol extraction components (0.110 g x L(-1)) < water-soluble polysaccharides components (0.168 g x L(-1)) < water extraction components (0.174 g x L(-1)) < water components after extraction (0.226 g x L(-1)) < total polysaccharides components (0.645 g x L(-1)). It is concluded that the different polarity components have different free radical scavenging activity and that provides a scientific basis for further search of the active ingredients and the activive mechanism.


Subject(s)
Antioxidants , Chemistry , Biphenyl Compounds , Chemistry , China , Ethnology , Drugs, Chinese Herbal , Chemistry , Free Radicals , Chemistry , Medicine, Chinese Traditional , Picrates , Chemistry , Plant Roots , Chemistry , Plant Stems , Chemistry , Smilax , Chemistry
16.
Acta Pharmaceutica Sinica ; (12): 530-534, 2014.
Article in Chinese | WPRIM | ID: wpr-245050

ABSTRACT

To investigate the effects of carbamazepine (CBZ) on the plasma concentrations of valproic acid (VPA) and its toxic metabolite 2-propyl-4-pentenoic acid (4-ene VPA) in epileptic patients, the plasma concentrations of VPA and 4-ene VPA were determined, and the effect of CBZ on pharmacokinetics of VPA was evaluated. All patients had been divided into two groups (VPA group, n = 87; and VPA+CBZ group, n = 19). As compared to VPA group, the combination of CBZ significantly (P < 0.01) decreased the trough concentration of VPA [VPA group, (69.5 +/- 28.8) microg x mL(-1); VPA+CBZ group, (46.3 +/- 25.6) microg x mL(-1)] and does-adjusted VPA trough concentration [VPA group, (4.89 +/- 2.21) microg x mL(-1) x mg(-1) x kg(-1); VPA+CBZ group, (3.14 +/- 1.74) microg x mL(-1) x mg(-1) x kg(-1)]. However, the addition of CBZ did not influence the concentration of 4-ene VPA. The present study revealed that coadministration of CBZ can reduce VPA plasma concentration and may impact VPA clinical effect, therefore therapeutic drug mornitoring of VPA should be used when combined use of CBZ and VPA.


Subject(s)
Adolescent , Adult , Anticonvulsants , Blood , Pharmacokinetics , Therapeutic Uses , Carbamazepine , Blood , Pharmacokinetics , Therapeutic Uses , Drug Interactions , Drug Therapy, Combination , Epilepsy , Blood , Drug Therapy , Fatty Acids, Monounsaturated , Blood , Female , Humans , Male , Valproic Acid , Blood , Pharmacokinetics , Therapeutic Uses , Young Adult
17.
Article in Chinese | WPRIM | ID: wpr-248201

ABSTRACT

<p><b>OBJECTIVE</b>To explore the mechanisms of the influx of calcium ions during the activation of ACh-sensitive BK channel (big conductance, calcium-dependent potassium channel) in type II vestibular hair cells of guinea pigs.</p><p><b>METHODS</b>Type II vestibular hair cells were isolated by collagenase type IA. Under the whole-cell patch mode, the sensitivity of ACh-sensitive BK current to the calcium channels blockers was investigated, the pharmacological property of L-type calcium channel activator-sensitive current and ACh-sensitive BK current was compared.</p><p><b>RESULTS</b>Following application of ACh, type II vestibular hair cells displayed a sustained outward potassium current, with a reversal potential of (-70.5 +/- 10.6) mV (x +/- s, n = 10). At the holding potential of -50 mV, the current amplitude of ACh-sensitive potassium current activated by 100 micromol/L ACh was (267 +/- 106) pA (n = 11). ACh-sensitive potassium current was potently sensitive to the BK current blocker, IBTX (iberiotoxin, 200 nmol/L). Apamin, the well-known small conductance, calcium-dependent potassium current blocker, failed to inhibit the amplitude of ACh-sensitive potassium current at a dose of 1 micromol/L. ACh-sensitive BK current was sensitive to NiCl2 and potently inhibited by CdCl2. NiCl2 and CdCl2 showed a dose-dependent blocking effect with a half inhibition-maximal response of (135.5 +/- 18.5) micromol/L (n = 7) and (23.4 +/- 2.6) micromol/L (n = 7). The L-type calcium channel activator, (-) -Bay-K 8644 (10 micromol /L), mimicked the role of ACh and activated the IBTX-sensitive outward current.</p><p><b>CONCLUSION</b>ACh-sensitive BK and L-type calcium channels are co-located in type II vestibular hair cells of guinea pigs.</p>


Subject(s)
Animals , Calcium Channels, L-Type , Guinea Pigs , Hair Cells, Vestibular , Metabolism , Large-Conductance Calcium-Activated Potassium Channels , Patch-Clamp Techniques
18.
Article in Chinese | WPRIM | ID: wpr-262884

ABSTRACT

<p><b>OBJECTIVE</b>To explore the feature of the ACh-sensitive potassium current in guinea pig cochlear outer hair cells.</p><p><b>METHODS</b>Cochlear outer hair cells of guinea pigs (n=38) were isolated by collagenase type IV. Under the whole-cell patch mode, the ions nature and the pharmacological properties of the ACh-sensitive potassium current were investigated by applying the inhibitors of calcium-dependent potassium currents and the inhibitors of nicotinic ACh receptor.</p><p><b>RESULTS</b>Following application of ACh, cochlear outer hair cells displayed a rapidly activating outward potassium current with a fast desensitized kinetic and a reversal (x +/- s) potential of (-67.3 +/- 8.2) mV (n=10). At the holding potential of -50 mV, the current amplitude of ACh-sensitive potassium current activated by 100 micronmol/L ACh was (506.6 +/- 186.3) pA (n=9). ACh-sensitive potassium current was sensitive to TEA (tetraethylammonium chloride, 10 mmol/L) and potently inhibited by the small conductance calcium-dependent potassium current (SK) blocker, apamin (1 micromol/L). Iberiotoxin (IBTX), the well-known blocker of big conductance calcium-dependent potassium current (BK), failed to inhibit the amplitude of the ACh-sensitive potassium current at the dose of 200 nmol/L. The dose for half-maximal response (EC50) of the ACh-sensitive potassium current was (33.5 +/- 5.7) micromol/L (n=7). The ACh-sensitive potassium current was sensitive to the GABA (gamma-aminobutyric acid)-A receptor blocker, bicuculline, and strongly inhibited by the selective blocker of the alpha 9-nicotinic ACh receptor, strychnine. Strychnine and bicuculline showed the dose-dependent blocking effect with a half inhibition-maximal response (IC50) of (22.3 +/- 2.6) nmol/L (n=7) and (1.2 +/- 0.4) micromol/L (n=6), respectively.</p><p><b>CONCLUSIONS</b>This work provides direct evidences that the ACh-sensitive SK current was present on guinea pig cochlear outer hair cells. The activation of the ACh-sensitive SK current was most possibly mediated by a alpha 9-nicotinic ACh receptor.</p>


Subject(s)
Animals , Guinea Pigs , Hair Cells, Auditory, Outer , Metabolism , Membrane Potentials , Patch-Clamp Techniques , Potassium , Metabolism , Pharmacology , Potassium Channels , Physiology , Receptors, Cholinergic , Metabolism
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