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Biomedical subjects

F Suzuki

Publications and source records attributed to F Suzuki.

At least 181 records · Page 10Linked to original sources
PubMed1997

Histopathologic study of islets of Langerhans in patients after gastrectomy.

In autopsy specimens removed after gastrectomy from patients who had survived for 2.5 to 40 years after surgery, we found hyalinization of the islets of Langerhans in 9 of 15 cases (60%) with Billroth's I anastomosis (B-I) and in 8 of 16 cases (50%) with Billroth's II anastomosis (B-II). The hyalinization in the postgastrectomy patients was significantly increased compared with that in controls (p < 0.01). The percentage of hyalinized islets of Langerhans in the 17 cases showing hyalinization ranged from 0.2% to 14.3%. The percentage increased relative to the period after gastrectomy in the B-I patients but not in those with B-II. The blood glucose level was mildly elevated in three B-I patients, whereas it was increased in only one patient with B-II. Hyalinization of the islets of Langerhans may be due to vagotomy or to excessive stimulus and hyperactivation of the islets. In any event, the islets of Langerhans in patients after gastrectomy were frequently replaced by hyalinization, which might cause impaired glucose tolerance.

Aged↗
PubMed1997

CD4- CD8- TCR alpha/beta+ suppressor T cells demonstrated in mice 1 day after thermal injury.

We have described previously that CD8+ CD11b+ TCR gamma/delta+ type 2 T cells (BA-type 2 T cells) and suppressor macrophages (Sup-Mł) are generated in spleens of mice 3 to 5 days (Sup-Mł) and 4 to 9 days (BA-type 2 T cells) after thermal injury. In the present study, an additional suppressor T cell, characterized as CD3+ CD4- CD8- TCR alpha/beta+ T cells (double negative suppressor T cells, DN Sup-T cells), was demonstrated in mice 1 day after thermal injury. DN Sup-T cells inhibited the proliferation of lymphocytes stimulated with allogeneic cells or a lectin in a mixed lymphocyte reaction, and produced both type 1 and type 2 cytokines (interferon-gamma, interleukin-2, interleukin-4, and interleukin-10) when they were stimulated in vitro with anti-CD3 monoclonal antibody. These results suggest that DN Sup-T cells express phenotypic properties similar to natural suppressor cells and cytokine-producing profiles different from type 1 (Th1 cells and CTLs) and type 2 T cells (Th2 cells and CD8+ type 2 T cells). DN Sup-T cells may play a role on the burn-associated immunosuppression appearing in the acute phase of thermally injured individuals.

Animals↗
PubMed1997

Case report: Clinical and virological analyses of a patient positive for hepatitis C virus-RNA by branched DNA assay but negative for anti-hepatitis C virus antibodies.

Infection with hepatitis C virus (HCV) is usually diagnosed by the presence of antibodies against fusion proteins or peptides derived from different regions of the HCV genome. However, a subgroup of patients with HCV viraemia are seronegative for antibody against hepatitis C virus (anti-HCV) by conventional antibody assays. We analysed serum samples from a patient with liver cirrhosis who tested negative for anti-HCV by a second-generation assay, but positive for HCV-RNA by reverse transcription polymerase chain reaction (RT-PCR) and branched DNA signal amplification. To identify possible mutations that could explain the failure of detection of anti-HCV by second-generation assay, PCR-amplified DNA fragments of the core region derived from the serum were cloned and sequenced. Nucleotide (nt) and amino acid (aa) sequence analyses (nt 1-486, aa 1-162) showed no mutations revealing stop codons, frame-shifts, deletions or insertions, but the presence of two amino acid substitutions (aa 75 and 91) when compared with HCV-J, a prototype strain of genotype 1b isolated from a Japanese patient. One of these two mutations (aa 75) was situated in the second hydrophilic domain of the core peptide, but analysis of the hydropathy profile showed only a little change. The two mutations were identical to those identified in other Japanese HCV isolates. The serum immunoglobulin level and T and B cell counts were normal in our patient. Our data suggest that the absence of anti-HCV in this patient was not due to mutations of major epitopes of HCV. Low-dose prednisolone administration just after transfusion may have induced immunological tolerance against HCV in this patient.

Aged↗
PubMed1997

Quantitative analysis of concealed conduction into accessory atrioventricular pathways in Wolff-Parkinson-White syndrome.

Concealed conduction is demonstrated to occur in an accessory AV pathway (AP). To test the hypothesis that anterograde and retrograde concealed conduction in the AP would have different characteristics, 35 consecutive patients with single APs were studied. The anterograde or retrograde ERP of the AP could be determined in 23 of those patients. Anterograde concealed conduction in the AP was assessed in the first 13 patients with retrograde AP conduction (6 APs with retrograde conduction only and 5 with both directions) (group A). Retrograde concealed conduction in the AP was evaluated in the remaining 10 patients with anterograde AP conduction (6 APs with anterograde conduction only and 4 with both directions) (group B). The concealed conduction in the AP was quantified by determining the ERP of the AP using a "probe" extrastimulus (Sp) introduced in the opposite chamber. The ERP was determined both during conventional extrastimulus (S1S2 method; ERPc) and during that with an Sp (S1SpS2 method; ERPp). The Sp was delivered before or after the last S1 with various S1Sp intervals. The ERPp was determined at each S1Sp interval. Three distinct patterns in concealed conduction in the AP were noted. In the first pattern, the ERPp was always shorter than the ERPc, whereas the reverse relation was noted in the second pattern. The third pattern showed a combination of the two. In group A, only the first pattern was noted. In group B, the first, second, and third patterns were noted in 4, 2, and 4 patients, respectively. The first pattern was noted only in septal APs and the second and third were seen only in left free-wall APs. The second pattern was seen in patients with retrograde AP conduction, whereas the third one was mainly noted in patients without retrograde AP conduction. These observations indicate that anterograde and retrograde concealed conduction in the AP have different characteristics. Shortening of the ERPp might be due to the "peeling back" phenomenon, and its lengthening might be caused by the presence of the inhomogeneous refractory periods of the AP.

Adult↗
PubMed1997

Glycyrrhizin, an active component of licorice roots, reduces morbidity and mortality of mice infected with lethal doses of influenza virus.

The antiviral effect of glycyrrhizin (GR), an active component of licorice roots, was investigated in mice infected with influenza virus A2 (H2N2). When mice that had been exposed to 10 50% lethal doses of the virus were treated intraperitoneally with 10 mg of GR per kg of body weight 1 day before infection and 1 and 4 days postinfection, all of the mice survived over the 21-day experimental period. At the end of this period, the mean survival time (in days) for control mice treated with saline was 10.5 days, and there were no survivors. The grade of pulmonary consolidations and the virus titers in the lung tissues of infected mice treated with GR were significantly lower than those in the lung tissues of infected mice treated with saline. GR did not show any effects on the viability or replication of influenza virus A2 in vitro. When splenic T cells from GR-treated mice were adoptively transferred to mice exposed to influenza virus, 100% of the recipients survived, compared to 0% survival for recipient mice inoculated with naive T cells or splenic B cells and macrophages from GR-treated mice. In addition, the antiviral activities of GR on influenza virus infection in mice were not demonstrated when it was administered to infected mice in combination with anti-gamma interferon (anti-IFN-gamma) monoclonal antibody. These results suggest that GR may protect mice exposed to a lethal amount of influenza virus through the stimulation of IFN-gamma production by T cells, because T cells have been shown to be producer cells of IFN-gamma stimulated with the compound.

Adoptive Transfer↗
PubMed1997

Insulin-like growth factors I and II are autocrine factors in stimulating proteoglycan synthesis, a marker of differentiated chondrocytes, acting through their respective receptors on a clonal human chondrosarcoma-derived chondrocyte cell line, HCS-2/8.

Both insulin-like growth factor (IGF)-I and IGF-II increased the synthesis of cartilage-type, large proteoglycan in a human chondrosarcoma-derived chondrocyte cell line, HCS-2/8. In contrast to the stimulatory effects of IGFs on costal chondrocytes of the young rabbit, the stimulatory effect of IGF-II on proteoglycan synthesis in HCS-2/8 cells was more potent than that of IGF-I. IGF-II, but not IGF-I, increased calcium influx into HCS-2/8 cells, and there was a close relation between the stimulation of proteoglycan synthesis and the calcium influx. [125I]IGF-I bound to HCS-2/8 cells, and this binding was competitively inhibited by low concentrations of unlabeled IGF-I, higher concentrations of IGF-II, and much higher concentrations of insulin. [125I]IGF-II also bound to the cells, and its binding was competitively inhibited by IGF-II and slightly inhibited by higher concentrations of IGF-I and much higher concentrations of insulin. When radioligand-receptor complexes were separated by SDS-PAGE and subjected to autoradiography, two major bands at 260 and 130 kDa were observed, which correspond to the IGF type II receptor (IGF-IIR) and the alpha subunit of the IGF type I receptor (IGF-IR), indicating the presence of both receptors. When confluent cultures of HCS-2/8 cells were maintained in serum-free medium, proteoglycan synthesis did not decrease unless the medium was repeatedly replaced. Conditioned medium of HCS-2/8 cells stimulated the HCS-2/8 cells to synthesize proteoglycans. RIA revealed that the cells produced both IGF-II and IGF-I. Transcripts of messenger RNAs of both IGF-I and IGF-II and both IGF-IR and IGF-IIR also were detectable by Northern analysis. Both anti-IGF-IR antibody and anti-IGF-II antibody inhibited proteoglycan synthesis. Mannose-6-phosphate, which is known to bind to IGF-IIR, stimulated proteoglycan synthesis, potentiated IGF-II-stimulated proteoglycan synthesis, and enhanced the binding affinity for IGF-II but not for IGF-I. Even in the presence of anti-IGF-IR antibody, IGF-II and mannose-6-phosphate stimulated proteoglycan synthesis in the cells. [Leu27]IGF-II, an IGF-II analogue with high affinity only for IGF-IIR, strongly stimulated proteoglycan synthesis in HCS-2/8 cells but [Arg54, Arg55]IGF-II, which binds to only IGF-IR, also stimulated proteoglycan synthesis in the cells. These findings indicate that IGF-I and IGF-II act as autocrine differentiation factors for this chondrocytic permanent cell line, HCS-2/8, mainly via respective receptors.

Analysis of Variance↗
PubMed1997

Transcatheter neodymium-yttrium-aluminum-garnet laser coagulation of canine ventricle using a balloon-tipped cardioscope.

The feasibility of transcatheter laser ablation of the canine left ventricle (LV) was tested using a newly developed cardioscope. In 17 anesthetized dogs, a combined laser-endoscope catheter, consisting of an endoscope encased in a 7-French flexible catheter with an inflatable and transparent balloon at the distal end, was introduced into the LV via the carotid artery. A 1064-nm neodymium-yttrium-aluminum-garnet (Nd:YAG) laser was delivered by laser optic fiber, which was introduced through the transport channel and positioned inside the saline-filled balloon. In 16 of 17 dogs, the endocardial surface of the LV was clearly observed. Laser energy totaling 500-5,000 J was applied sequentially in 13 dogs and laser irradiation was completed in all but 2 of the dogs. The excised hearts revealed well-demarcated oval-shaped lesions 2.5-9.5 mm deep in 7 of 11 dogs. Histologic sections revealed coagulation necrosis surrounded by a rim of contraction band necrosis. Thus, transballoon laser photocoagulation of the beating LV is feasible. The newly combined laser-endoscope catheter, which is still in its preliminary stages and needs to be improved to increase the success rate of photocoagulation, appears to be a promising alternative modality for catheter ablative therapy for ventricular tachycardia.

Animals↗
PubMed1997

Involvement of alpha5beta1 integrin in matrix interactions and proliferation of chondrocytes.

Integrins are cell surface receptors involved in cellular processes including adhesion, migration, and matrix assembly. In the present study, we analyzed the possible involvement of alpha 5 beta 1 integrin in the regulation of chondrocyte adhesion, spreading, and proliferation. We found that rabbit growth plate chondrocytes were able to attach to substrates coated with type I collagen, type II collagen, or fibronectin within 24 h of culture. During this time period, attachment to fibronectin appeared to be dependent on alpha 5 beta 1 integrin, whereas adhesion to collagens was not. By day 3 of culture, chondrocytes spread onto all the substrates tested. We found that regardless of the nature of the substrate, cell spreading was reversed by treatment with RGD peptide or antibodies against alpha 5 beta 1 or fibronectin, indicating that cell spreading involved alpha 5 beta 1 and fibronectin endogenously produced and deposited by the chondrocytes themselves. Colony formation by chondrocytes in soft agar was inhibited by treatment with RGD peptides or BIIG2, an antibody that interferes with alpha 5 beta 1 integrin-ligand interactions. Furthermore, DNA content was decreased by treatment with anti-fibronectin antibody in micromass culture of chondrocytes. Immunohistochemical analysis on tissue sections revealed that the alpha 5 subunit was particularly abundant in the proliferative and hypertrophic zones of growth plate. The results of the study indicate that alpha 5 beta 1 integrin plays multiple roles in chondrocyte behavior and function and appears to be involved in the regulation of both chondrocyte-matrix interactions and proliferation.

Animals↗
PubMed1997

Cellular hypertrophy and calcification of embryonal carcinoma-derived chondrogenic cell line ATDC5 in vitro.

During the process of endochondral bone formation, proliferating chondrocytes give rise to hypertrophic cells, which then deposit a mineralized matrix to form calcified cartilage prior to replacement by bone. Previously, we reported that a clonal cell line, ATDC5, undergoes efficient chondrogenic differentiation through a cellular condensation stage. Here we report that the differentiated ATDC5 cells became hypertrophic at the center of cartilage nodules, when the cells ceased to grow. Formation of hypertrophic chondrocytes took place in association with type X collagen gene expression and a dramatic elevation of alkaline phosphate (ALPase) activity. After 5 weeks of culture, mineralization of the culture could be discerned as Alizarin red-positive spots, which spread throughout the nodules even in the absence of beta-glycerophosphate. Electron microscopy and electron probe microanalysis revealed that calcification was first initiated at matrix vesicles in the territorial matrix and that it advanced progressively along the collagen fibers in a manner similar to that which occurs in vivo. The infrared spectrum of the mineralized nodules indicated two absorption doublets around 1030 cm-1 and 600 cm-1, which are characteristic of apatitic mineral. Calcifying cultures of ATDC5 cells retained responsiveness to parathyroid hormone (PTH): PTH markedly inhibited elevation of ALPase activity and calcification in the culture in a dose-dependent manner. Thus, we demonstrated that ATDC5 cells keep track of the multistep differentiation process encompassing the stages from mesenchymal condensation to calcification in vitro. ATDC5 cells provide an excellent model to study the molecular mechanism underlying regulation of cartilage differentiation during endochondral bone formation.

Alkaline Phosphatase↗
PubMed1997

[Detection of HPV-DNA in the various uterocervical lesion by the in situ polymerase chain reaction].

The causal association of human papilloma virus(HPV) with cervical cancer has been supported by multiple lines of evidence. Therefore, in the case of dysplasia, the presence of HPV-DNA should be detected and its subtypes identified. This is important in the determination of the prognosis for cervical disease. We reported a study in which the localization and types of HPV in cervical diseases was identified by in situ polymerase chain reaction(PCR), using biotin-labelled DNA probes. The in situ PCR, used by us was modified of Nuovo's method. We used biopsy materials of 18 CIN and 9 SCC cases(total 27 cases), all of which had been detected HPV-DNA by Southern blot hybridization, but not detected by in situ hybridization. A positive intranuclear reaction was detected in 13 of 18 CIN cases and 6 of 9 SCC cases(total 19 positive cases). Molecular biological techniques are the most reliable methods for detecting specific tumor genes and virus DNA. In situ hybridization has the advantage of enabling recognition of the cellular localization of the DNA in histologic specimens, but its sensitivity in inferior to the other techniques such as Southern blot, Dot blot and PCR. In situ PCR method possesses the advantages of both PCR and in situ hybridization in being highly sensitive and enabling visualization of the cellular localization of the DNA. In our present study, we succeeded to detect HPV-DNA in cervical biopsies of CIN and SCC cases by the in situ PCR.

Adolescent↗
PubMed1997

A histopathologic study of localized portal hypertension as a consequence of chronic pancreatitis.

OBJECTIVE: To evaluate the mechanism of localized portal hypertension associated with stenosis or obstruction of the splenic vein in chronic alcoholic pancreatitis. DESIGN: Surgical and autopsy specimens from 12 patients with clinically diagnosed chronic alcoholic pancreatitis were examined histopathologically. Autopsy specimens of 10 normal pancreases served as control tissues. RESULTS: In tissues from 11 of the 12 patients with chronic-alcoholic pancreatitis, fibrosis in the pancreatic parenchyma continuously extended to the wall of the splenic vein; organized thrombus formation with recanalization was found in five patients, phlebosclerosis in four, and no changes were found in two. In two of the five patients with organized thrombus formation in the splenic vein, localized portal hypertension had been clinically diagnosed because of splenomegaly and varicose veins in the fundus of the stomach, but it was not accompanied by liver cirrhosis. In the control tissues, fibrosis was not observed in the peripancreatic tissue or the area surrounding the wall of the splenic vein. CONCLUSION: We regard localized portal hypertension due to stenosis or obstruction of the splenic vein as one of the consequences of peripancreatic fibrosis in chronic alcoholic pancreatitis.

Adult↗
PubMed1997

L-DOPA cyclohexyl ester is a novel stable and potent competitive antagonist against L-DOPA, as compared to L-DOPA methyl ester.

We explore stable potent competitive antagonists against L-DOPA. In anesthetized rats, DOPA cyclohexyl ester (DOPA CHE) (30-100 ng) microinjected in depressor sites of the nucleus tractus solitarii dose-dependently shifted the dose-response-curve for L-DOPA (18-300 ng) to the right, with DOPA CHE (100 ng)-induced slight reduction of the maximum response. DOPA methyl ester (DOPA ME) at 100 ng also produced competitive antagonism. Antagonistic activity of DOPA CHE (100 ng) was similar to that of DOPA ME (300 ng). DOPA CHE is suitable for the purpose of screening.

Animals↗
PubMed1997

Pace-mapping conduction delay at reentry circuit sites of ventricular tachycardia after myocardial infarction.

This study was carried out to determine the relationship of conduction delay during pace-mapping, as indicated by the stimulus to QRS interval to different reentry circuit sites and bystanders, as identified by entrainment criteria, in patients with ventricular tachycardia late after myocardial infarction. Catheter mapping and ablation were performed in 40 patients with ventricular tachycardia after myocardial infarction. Data were retrospectively analyzed from 122 endocardial sites which met the following the criteria: a 12-lead electrocardiogram was recorded during pace-mapping, ventricular tachycardia was then induced and entrained by pacing to classify the type of the site relative to the reentry circuit exit. By entrainment criteria 77 sites were in the reentry circuit (28 exit sites, 49 other circuit sites) and 45 sites were bystanders not in the reentry circuit. The average stimulus conduction delay at central/proximal sites was 103 +/- 43 ms, which was significantly longer than at exit (57 +/- 31 ms), outer loop sites (57 +/- 32 ms), and bystander sites (57 +/- 37 ms); P < 0.05. Pace-mapping revealed evidence of greater conduction delay at sites proximal to the reentry circuit exit, consistent with slow conduction between these regions and the border of the infarct. Exit sites and outer loop sites were more likely to be located along the border of the infarct, with less conduction delay evident during pace-mapping.

Cardiac Pacing, Artificial↗
PubMed1996

Functional domains of transcription factor hGABP beta1/E4TF1-53 required for nuclear localization and transcription activation.

Transcription factor E4TF1 is the human homolog of GABP and has been renamed hGABP (human GABP). hGABP is composed of two types of subunits; hGABP beta1/E4TF1-53 and the ets-related protein hGABP alpha/E4TF1-60. Both bind together to form an (alpha)2(beta1)2 heterotetrameric complex on DNA and activate transcription at specific promoters in vitro. Tetramer formation depends on two regions of hGABP beta1; the N-terminal region containing the Notch/ankyrin-type repeats is necessary for binding to hGABP alpha and the C-terminal region is necessary for homodimerization. In this report, we constructed various deletion mutants of hGABP beta1 in order to delimit the functional regions required for nuclear localization and transcription activity. We found that hGABP beta1 localization in the nucleus is dependent on a region located between amino acids 243 and 330 and that the presence of hGABP beta1 influences the efficiency of hGABP alpha transport into the nucleus. Next, we demonstrated that the hGABP complex composed of alpha and beta1 subunits activates transcription from the adenovirus early 4 promoter in vivo. This transcription activation needs the C-terminal region of hGABP beta1 and is consistent with results obtained with the in vitro assay. Furthermore, site-directed mutagenesis analysis of the C-terminal region reveals that the alpha-helix structure and the leucine residues are important for formation of a heterotetrameric complex with hGABP alpha in vitro and for transcription activation in vivo. These results suggest that hGABP beta1 stimulates transcription as part of a heterotetrameric complex with hGABP alpha in vivo.

Animals↗
PubMed1996

A novel growth-promoting factor derived from fetal bovine cartilage, chondromodulin II. Purification and amino acid sequence.

During endochondral bone formation, cartilage cells show increased matrix synthesis and rapid proliferation. We found that cartilage matrix contains at least two types of heparin binding growth-promoting components. One, with a higher affinity to heparin, was identified as chondromodulin I (Hiraki, Y., Tanaka, H., Inoue, H. , Kondo, J., Kamizono, A., and Suzuki, F. (1991) Biochem. Biophys. Res. Commun. 175, 871-977). In this study, we isolated a novel growth-promoting component, chondromodulin II, which has a lower heparin affinity, from the dissociative extracts of fetal bovine epiphyseal cartilage. Chondromodulin II stimulated the proteoglycan synthesis in rabbit cultured growth plate chondrocytes, an expression of the differentiated phenotype of chondrocytes. It also stimulated DNA synthesis in chondrocytes in both the absence and the presence of fibroblast growth factor-2. The apparent molecular mass of chondromodulin II on SDS-polyacrylamide gel electrophoresis was 16 kDa. Its complete amino acid sequence was determined by overlapping sequences of the peptides released by endopeptidase digestion and CNBr cleavage. Chondromodulin II consists of 133 amino acids (calculated Mr = 14,548). The sequence was unique but homologous to the repeats 1 and 2 of the deduced amino acid sequence of the chicken mim-1 gene, which is specifically transactivated by the v-Myb oncogene product in promyelocytes. We also found a minor component with a higher heparin affinity, chondromodulin III, in cartilage extracts. Chondromodulin III stimulated DNA synthesis in chondrocytes in vitro, and its N-terminal sequence was identical with ribosomal protein L31 lacking the N-terminal three amino acids. These findings suggest that the growth and differentiation of chondrocytes are regulated by multiple components in the cartilage matrix.

Acetyltransferases↗
PubMed1996

Promotion of sleep mediated by the A2a-adenosine receptor and possible involvement of this receptor in the sleep induced by prostaglandin D2 in rats.

A 6-hr continuous infusion of 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenos ine (CGS21680), a selective A2a-adenosine agonist, into the subarachnoid space underlying the ventral surface region of the rostral basal forebrain, which has been defined as the prostaglandin (PG) D2-sensitive sleep-promoting zone, at rates of 0.02, 0.2, 2.0, and 12 pmol/min increased slow-wave sleep (SWS) and paradoxical sleep (PS) in a dose-dependent manner up to 183% and 202% of their respective baseline levels. The increments produced by the infusion of CGS21680 at 0.2 and 2.0 pmol/min were totally diminished when the rats had been pretreated with an i.p. injection of (E)-1,3-dipropyl-7-methyl-8-(3,4-dimethoxystyryl)xanthine (KF17837; 30 mg/kg of body weight), a selective A2-adenosine antagonist. In contrast, the infusion of N6-cyclohexyladenosine (CHA), a selective A1-adenosine agonist, at 2 pmol/min significantly suppressed SWS before causing an increase in SWS, and a decrease in PS was also markedly visible. Essentially the same effects of CGS21680 and CHA were observed when these compounds were administered to the parenchymal region of the rostral basal forebrain through chronically implanted microdialysis probes. Thus, we clearly showed that stimulation of A2a-adenosine receptors in the rostral basal forebrain promotes SWS and PS. Furthermore, i.p. injections of KF17837 at 30 and 100 mg/kg of body weight dose-dependently attenuated the magnitude of the SWS increase produced by the infusion of PGD2 into the subarachnoid space of the sleep-promoting zone, thus indicating that the A2a-adenosine receptors are crucial in the sleep-promoting process triggered by PGD2.

Adenosine↗
PubMed1996

Subtype selectivity of a new alpha 1-adrenoceptor antagonist, JTH-601: comparison with prazosin.

The existence of alpha 1-adrenoceptors with low affinity for prazosin (alpha 1L group: alpha 1L and alpha 1N subtypes) has been proposed in addition to alpha 1-adrenoceptor subtypes with high affinity for prazosin (alpha 1H group: alpha 1A, alpha 1B and alpha 1D subtypes). A newly synthesized alpha 1-adrenoceptor antagonist, JTH-601 (N-(3-hydroxy-6-methoxy-2,4,5-trimethylbenzyl)-N-methyl-2-(4-hydro xy-2-isopropyl-5-methyl-phenoxy) ethylamine hemifumarate) showed approximately a 10 times higher affinity for the alpha 1L group, a similar affinity for the alpha 1A subtype, but a more than 10 times lower affinity for the alpha 1B and alpha 1D subtypes when compared with prazosin. These results provide a further pharmacological evidence that alpha 1-adrenoceptors with low affinity for prazosin exist in addition to those with high affinity for prazosin, suggesting that JTH-601 may be useful for characterising the alpha 1-adrenoceptor subtypes.

Adrenergic alpha-Antagonists↗