Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"Heterogeneous expression of tandem-pore K+ channel genes in adult and embryonic rat heart quantified by real-time polymerase chain reaction.","authors":"W Liu,&nbsp;D A Saint","doi":"10.1111/j.1440-1681.2004.03964.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2004.03964.x","url":null,"abstract":"<p><p>1. Many members of the tandem-pore K+ channel gene family have been reported to be present in cardiac cells. However, the pattern of gene expression of these channels in the heart is a matter of some dispute. 2. Here, we used reverse transcription and real-time quantitative polymerase chain reaction to investigate the pattern of gene expression of nine members of the tandem-pore K+ channel genes in adult and embryonic rat heart. The genes (TWIK-1, TWIK-2, TASK-1, TASK-2, TASK-3, TREK-1, TREK-2, TRAAK and KCNK6) were quantified, relative to glyceraldehyde-3-phosphate dehydrogenase (GADPH), in all four chambers of adult rat hearts and in the ventricles of embryonic rat hearts. 3. All these genes were detected in at least one chamber of the heart, with a predominance of TWIK-2, TASK-1 and TREK-1 expression. The expression of TWIK-2 was higher in the right atrium than in other cardiac chambers, TASK-1 was expressed more in atria than in ventricles and TREK-1 was highly expressed in the right ventricle. 4. The expression levels of the three predominant genes in embryonic rat ventricle are much lower than their expression in adult rat ventricles. 5. The physiological implications of the differential gene expression of the tandem-pore K+ channels is discussed.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"31 3","pages":"174-8"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2004.03964.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24432546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased oxidative stress in prehepatic portal hypertensive rat livers following the induction of diabetes.","authors":"P Evelson,&nbsp;S Llesuy,&nbsp;E Filinger,&nbsp;R R Rodriguez,&nbsp;A Lemberg,&nbsp;C Scorticati,&nbsp;M Susemihl,&nbsp;I Villareal,&nbsp;J M Polo,&nbsp;H Peredo,&nbsp;J C Perazzo","doi":"10.1111/j.1440-1681.2004.03963.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2004.03963.x","url":null,"abstract":"<p><p>1. Oxidative stress (OS) is a biological entity indicated as being responsible for several pathologies, including diabetes. Diabetes can also be associated with human cirrhosis. Portal hypertension (PH), a major syndrome in cirrhosis, produces hyperdynamic splanchnic circulation and hyperaemia. The present study was designed to investigate the occurrence of OS in prehepatic PH rat livers following the induction of diabetes. 2. Five groups of rats were used: control, sham operated, chronic diabetes (induced with a single dose of streptozotocin at 60 mg/kg, i.p.), prehepatic PH and chronic diabetic plus prehepatic PH. The occurrence of OS was determined in liver homogenates by measuring hydroperoxide-initiated chemiluminescence and the activity of anti-oxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase). 3. Prehepatic PH produced a significant increase in hydroperoxide-initiated chemiluminescence in the liver compared with control and sham-operated rats, whereas the liver in chronic diabetic rats showed no difference. However, chemiluminescence values decreased almost by 50% in the chronic diabetic plus prehepatic PH group. Concomitantly, the activities of the anti-oxidant enzymes in chronic diabetes, prehepatic PH and chronic diabetic plus prehepatic PH groups were decreased (P < 0.05 vs control and sham-operated groups). 4. Livers from the chronic diabetic group did not show any evidence of the occurrence of OS, whereas the prehepatic PH group showed the occurrence of OS. The association of PH and chronic diabetes resulted in a significant decrease in the occurrence of OS, which could be explained by an anti-oxidant response to an OS.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"31 3","pages":"169-73"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2004.03963.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24433879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteins of the bcl-2 family in apoptosis signalling: from mechanistic insights to therapeutic opportunities.","authors":"Shing-Leng Chan,&nbsp;Victor C Yu","doi":"10.1111/j.1440-1681.2004.03975.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2004.03975.x","url":null,"abstract":"<p><p>1. Proteins of the Bcl-2 family are central regulators of apoptosis and are thought to act primarily on the mitochondria. 2. Members of the Bcl-2 family possess either anti-apoptotic or pro-apoptotic function. They are characterized by the presence of conserved sequence motifs, known as Bcl-2 homology (BH) domains. Anti-apoptotic members share all four BH domains, designated as BH1-4; the multidomain pro-apoptotic members contain BH1-3 domains, whereas another subgroup of pro-apoptotic members only have a BH3 domain. 3. The BH3-only proteins act as sensors for distinct apoptosis pathways, whereas multidomain pro-apoptotic Bax and Bak are executioners of death orders relayed by the BH3-only proteins. 4. Anti-apoptotic Bcl-2 family members appear to function, at least in part, by interacting with and antagonizing pro-apoptotic family members. The BH1-3 domains of BclXL form an elongated hydrophobic groove, which is the docking site for the BH3 domains of pro-apoptotic binding partners. 5. The deregulation of the various Bcl-2 proteins has been implicated in many pathological conditions. 6. Knowledge derived from the understanding of the function and regulation of the Bcl-2 family of proteins has allowed us to contemplate new therapeutic strategies for diseases where apoptosis signalling mechanisms can potentially be manipulated. 7. The anti-apoptotic Bcl-2 members have been targeted successfully using an antisense approach, BH3-peptides and small molecular weight chemicals that are inhibitors of their anti-apoptotic function.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"31 3","pages":"119-28"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2004.03975.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24433872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxcarbazepine antinociception in animals with inflammatory pain or painful diabetic neuropathy.","authors":"Sumiyoshi Kiguchi,&nbsp;Takahiro Imamura,&nbsp;Kiyoshi Ichikawa,&nbsp;Masami Kojima","doi":"10.1111/j.1440-1681.2004.03950.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2004.03950.x","url":null,"abstract":"<p><p>1. Diabetic neuropathy is one of the most frequent complications of diabetes mellitus. However, the mechanisms underlying these disorders are not yet well defined and it has been reported that currently available analgesics have hardly any ameliorating effect on painful diabetic neuropathy. 2. The purpose of the present study was to evaluate the antinociceptive effect of oxcarbazepine (OCBZ), a keto derivative of carbamazepine (CBZ), in animal models generally used in pain research and in rats and mice with streptozotocin (STZ)-induced diabetes. In addition, we compared the effect of OCBZ with those of CBZ, mexiletine and morphine. 3. Diabetes was induced by injection of STZ at a dose of 300 mg/kg (i.p.) in mice and 50 mg/kg (i.v.) in rats. Experiments were conducted 2 weeks after STZ injection and those animals with a serum glucose level above 400 mg/dL were used for data analysis. Antinociceptive effects of the drugs were evaluated by the paw withdrawal test (normal, STZ-induced diabetic and carrageenin-injected rats), tail-flick test (normal and STZ-induced diabetic mice) and nociceptive behaviour (formalin-injected mice). 4. In the present study, diabetic mice showed thermal hyperalgesia and diabetic rats exhibited mechanical hyperalgesia. From these results, the STZ-induced diabetic animals used in the present study were found to be suitable for research on painful diabetic neuropathy. In STZ-induced diabetic animals, the antinociceptive effects of OCBZ, CBZ and mexiletine were facilitated, whereas the effect of morphine was attenuated, compared with effects in normal animals. 5. Oxcarbazepine inhibited the formalin-induced biphasic pain responses and increased the nociceptive threshold in the case of carrageenin-induced hyperalgesia. In view of these results, inhibition of substance P-mediated pain transmission may be involved in the antinociceptive action of OCBZ. 6. These results indicate that OCBZ has an analgesic action and is a possible therapeutic agent for the treatment of neuropathic pain, such as occurs in painful diabetic neuropathy.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"31 1-2","pages":"57-64"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2004.03950.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24192623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Actions of the anti-oestrogen agent clomiphene on outward K+ currents in rat ventricular myocytes.","authors":"John J Borg,&nbsp;Jules C Hancox,&nbsp;Dayle S Hogg,&nbsp;Andrew F James,&nbsp;Roland Z Kozlowski","doi":"10.1111/j.1440-1681.2004.03956.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2004.03956.x","url":null,"abstract":"<p><p>1. The effects of clomiphene (CLM) on cardiac outward K+ current components from rat isolated ventricular myocytes were investigated using the whole-cell patch-clamp technique. Clomiphene (10 micromol/L) significantly inhibited both peak (Ipeak) and end-pulse (Ilate) outward currents (elicited by a 500 msec voltage step from -40 to +50 mV in the presence of K+-containing intracellular and extracellular solutions) by approximately 37% (n = 6; P < 0.01) and 49% (n = 6; P < 0.01), respectively. In contrast, CLM had no effect on outward currents when K+-free solutions were used. 2. A double-pulse protocol and Boltzmann fitting were used to separate individual K+ current components on the basis of their voltage-dependent inactivation properties. At potentials positive to -80 mV, two inactivating transient outward components (Ito) and (IKx) and a non-inactivating steady state component (Iss) could be distinguished. 3. Clomiphene inhibited both Ito and Iss. The maximal block of Ito and Iss induced by CLM (100 micromol/L) was approximately 61% (n = 5) and 43% (n = 5) with IC50 values of 1.54 +/- 0.39 and 2.2 +/- 0.4 micromol/L, respectively. In contrast, the peak magnitude of IKx was unaltered by CLM, although its time-course of inactivation was accelerated. 4. Further experiments whereby myocytes were superfused with the vasoactive peptide endothelin (ET)-1 (20 nmol/L) revealed that CLM (10 micro mol/L) completely abolished the ET-1-sensitive component of Iss. 5. Our findings demonstrate, for the first time, the effects of CLM on distinct cardiac K+ current components and show that CLM modulates the voltage-gated K+ current components Ito and IKx and inhibits the steady state outward current Iss in rat ventricular myocytes.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"31 1-2","pages":"86-95"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2004.03956.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24192622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiorespiratory effects of intravenous N-methyl-D-aspartate challenge in anaesthetized rats.","authors":"Katarzyna Kaczyñska,&nbsp;Małgorzata Szereda-Przestaszewska","doi":"10.1111/j.1440-1681.2004.03958.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2004.03958.x","url":null,"abstract":"<p><p>1. Experiments were performed to determine the effects of systemic application of N-methyl-d-aspartate (NMDA) on respiratory variables and blood pressure in 22 urethane/chloralose-anaesthetized, spontaneously breathing rats. 2. Bolus injection of NMDA at a dose of 27 micro mol/kg, i.v., in neurally intact rats evoked a depression of breathing, most apparent at 30 s, comprising a decrease in tidal volume (P < 0.001) and respiratory rate (P < 0.001). The expiratory apnoea appeared in three intact rats only. 3. The respiratory effects of NMDA were independent of the vagal integrity between lungs and the nodose ganglia. Elimination of supranodose connection to the medulla reduced the prolongation of the expiratory time (P < 0.01). 4. N-Methyl-d-aspartate induced an initial rise in blood pressure followed by hypotension in rats treated by infra- and supranodose vagotomy. 5. It is concluded that the respiratory response to systemic NMDA challenge occurs beyond lung vagi and indicates that neurons of the nodose ganglia contribute to NMDA inhibition of the expiratory time.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"31 1-2","pages":"101-6"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2004.03958.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24194244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipophilicity affects the pharmacokinetics and toxicity of local anaesthetic agents administered by caudal block.","authors":"Alejandro A Nava-Ocampo,&nbsp;Angélica M Bello-Ramírez","doi":"10.1111/j.1440-1681.2004.03961.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2004.03961.x","url":null,"abstract":"<p><p>1. Drugs administered into the epidural space by caudal block are cleared by means of a process potentially affected by the lipophilic character of the compounds. 2. In the present study, we examined the relationship between the octanol-water partition coefficient (log Poct) and the time to reach the maximum plasma drug concentration (tmax) of lignocaine, bupivacaine and ropivacaine administered by caudal block in paediatric patients. We also examined the relationship between log Poct and the toxicity of these local anaesthetic agents in experimental models. The tmax and toxicity data were obtained from the literature. 3. Ropivacaine, with a log Poct of 2.9, exhibited a tmax of 61.6 min. The tmax of lignocaine, with a log Poct of 2.4, and bupivacaine, with a log Poct of with 3.4, were approximately 50% shorter than ropivacaine. At log Poct of approximately 3.0, the toxicity of these local anaesthetic agents was substantially increased. The relationship between log Poct and the convulsive effect in dogs was similar to the relationship between log Poct and the lethal dose in sheep. 4. With local anaesthetic agents, it appears that the relationship between log Poct and drug transfer from the epidural space to the blood stream is parabolic, being the slowest rate of transference at log Poct 3.0. Toxicity, due to plasma availability of these local anaesthetic agents, seems to be increased at log Poct equal or higher than 3.0 secondary to the highest transfer from plasma into the central nervous system.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"31 1-2","pages":"116-8"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2004.03961.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24194246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A < 1.7 cM interval is responsible for Dmo1 obesity phenotypes in OLETF rats.","authors":"Takeshi K Watanabe,&nbsp;Shiro Okuno,&nbsp;Yuki Yamasaki,&nbsp;Toshihide Ono,&nbsp;Keiko Oga,&nbsp;Ayako Mizoguchi-Miyakita,&nbsp;Hideo Miyao,&nbsp;Mikio Suzuki,&nbsp;Hiroshi Momota,&nbsp;Yoshihiro Goto,&nbsp;Hiroichi Shinomiya,&nbsp;Haretsugu Hishigaki,&nbsp;Isamu Hayashi,&nbsp;Toshihiro Asai,&nbsp;Shigeyuki Wakitani,&nbsp;Toshihisa Takagi,&nbsp;Yusuke Nakamura,&nbsp;Akira Tanigami","doi":"10.1111/j.1440-1681.2004.03959.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2004.03959.x","url":null,"abstract":"<p><p>1. Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes of male Otsuka Long Evans Tokushima Fatty (OLETF) rats. 2. Our congenic lines, produced by transferring Dmo1 chromosomal segments from the non-diabetic Brown Norway (BN) rat into the OLETF strain, have confirmed the strong, wide-range therapeutic effects of Dmo1 on dyslipidaemia, obesity and diabetes in the fourth (BC4) and fifth (BC5) generations of congenic animals. Analysis of a relatively small number of BC5 rats (n = 71) suggested that the critical Dmo1 interval lies within a < 4.9 cM region between D1Rat461 and D1Rat459. 3. To confirm the assignment of the Dmo1 critical interval, we intercrossed BC5 animals to produce a larger study population (BC5:F1 males; n = 406). For the present study, we used bodyweight at 18 weeks of age as an index of obesity; this phenotype is representative of the closely associated dyslipidaemia and hyperglycaemia phenotypes. 4. Interval mapping assigned logarithm of odds (LOD) peaks at the D1Rat90 marker (LOD = 9.11). One LOD support interval lies within the < 1.7 cM region between D1Rat461 and D1Rat459. 5. This large intercross study confirms that Dmo1 is likely localized within the interval.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"31 1-2","pages":"110-2"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2004.03959.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24194243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric oxide promotes mitogen-induced dna synthesis in human dermal fibroblasts through cGMP.","authors":"Gursev S Dhaunsi,&nbsp;Pinar T Ozand","doi":"10.1111/j.1440-1681.2004.03948.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2004.03948.x","url":null,"abstract":"<p><p>1. Nitric oxide (NO) is a free radical with multiple functions in cellular pathophysiology. Nitric oxide has been proven to play an important role in wound healing; however, the mechanisms by which NO may promote wound healing are not clearly understood. We have investigated the effect of NO on growth factor-induced DNA synthesis in human dermal fibroblasts to suggest interactions between growth factors and NO as a possible mechanism for the role of NO in wound healing. 2. The NO donor sodium nitroprusside (SNP) significantly (P < 0.001) increased fetal bovine serum-induced thymidine incorporation into the DNA of human dermal fibroblasts. The maximal comitogenic concentration of SNP (100 micro mol/L) was also found to significantly (twofold; P < 0.01) enhance fibroblast growth factor- or platelet-derived growth factor-induced DNA synthesis. 3. Nitric oxide treatment significantly increased the production of cGMP. 8-Bromo-cGMP, a stable structural analogue of cGMP, was found to markedly potentiate (P < 0.001) the growth factor-induced DNA synthesis. 4. This study concludes that NO and cGMP promote growth factor-induced DNA synthesis in dermal fibroblasts, suggesting another possible mechanism by which NO may promote skin wound healing.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"31 1-2","pages":"46-9"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2004.03948.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24192126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basal transcriptional regulation of rat AT1 angiotensin II receptor gene expression.","authors":"Toshie Kambe,&nbsp;Naoki Kinjyo,&nbsp;Hitoshi Hiruki,&nbsp;Takao Kubo","doi":"10.1111/j.1440-1681.2004.03957.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2004.03957.x","url":null,"abstract":"<p><p>1. Angiotensin II AT1A receptors are thought to play an important role in the development of hypertension. The transcriptional factor Sp1 is a ubiquitous transcriptional factor associated with GC-rich promoters and involved in basal promoter activity. 2. To examine basal transcriptional levels regulation of the rat AT1A receptor gene, we determined whether two GC-box-related regions within 100 bp of the rat AT1A receptor gene promoter are involved in the basal expression of the gene in A10 cells, a vascular smooth muscle cell line. 3. The electrophoretic mobility shift assay demonstrated that incubation of the -98/-79 region and -58/-34 region sequence oligonucleotides with nuclear extracts of rat hypothalamus, liver and adrenal formed DNA-protein complexes and that the addition of unlabelled oligonucleotides containing the Sp1 consensus sequence blocked the formation of the DNA-protein complex. The addition of antibody against Sp1 also blocked the formation of the DNA-protein complex. 4. The promoter/luciferase reporter assay demonstrated that the reporter activity of AT1A receptor promoters mutated either within the -98/-79 or the -58/-34 region was lower than that of intact AT1A receptor promoters. 5. The promoter activity of AT1A receptor promoters mutated within those two regions was lower than that of promoters mutated within either the -98/-79 or the -58/-34 region. 6. These findings suggest that GC-box-regulated sequences within the -98/-79 region and the -58/-34 region are additively involved in basal expression level of the AT1A receptor gene in A10 cells.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"31 1-2","pages":"96-100"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2004.03957.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24192624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}