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PubMed2006

Comparison of three radioligands for the labelling of human beta-adrenoceptor subtypes.

We have compared the ability of three radioligands, [(125)I]-cyanopindolol, [(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol, to label the three human beta-adrenoceptor subtypes. Saturation and competition binding experiments were performed using membrane preparations from Chinese hamster ovary cells stably transfected with the three subtypes. While [(3)H]-CGP 12,177 had very similar affinity for beta(1)- and beta(2)-adrenoceptors (about 40 pM), [(125)I]-cyanopindolol and [(3)H]-dihydroalprenolol had 4- to 6-fold higher affinity for beta(2)- as compared to beta(1)-adrenoceptors (10 vs 45 and 187 vs 1,021 pM, respectively). The affinity of [(125)I]-cyanopindolol at beta(3)-adrenoceptors was considerably lower (440 pM) than at the other two subtypes. The beta(3)-adrenoceptor affinity of [(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol was so low that it could not be estimated within the tested range of radioligand concentrations (up to 4,000 pM and 30,000 pM for [(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol, respectively). We conclude that all three radioligands are ill-suited to label beta(3)-adrenoceptors, particularly in preparations co-expressing multiple subtypes. In the absence of alternatives, [(125)I]-cyanopindolol appears the least unsuitable to label beta(3)-adrenoceptors. There is a need for high-affinity radioligands which are either selective for beta(3)-adrenoceptors or reasonably non-selective among all three beta-adrenoceptor subtypes.

Adrenergic beta-Agonists↗
PubMed2001

Analysis of ligand activation of alpha 2-adrenoceptor subtypes under conditions of equal G alpha protein stoichiometry.

Variations in the measurement of ligand's intrinsic activity between receptor subtypes is a common consequence of unequal receptor:G protein density ratios. We have investigated ligand activation at the alpha2-adrenoceptor (alpha2-AR) subtypes under defined expression conditions of one receptor molecule for one Galpha protein molecule using fusion proteins. Fusion between either a wt alpha2C AR or a mutant Thr382Lys alpha2C AR and a chimeric Galphaq/il protein displayed robust, transient (-)-adrenaline-mediated Ca2+ responses with similar potencies (pEC50: 7.78 and 7.66) and kinetic properties. A comparison of the intrinsic activities of alpha2 AR agonists found d-medetomidine to be the only compound with an efficacy similar to that of (-)-adrenaline. The Ca2+ responses as mediated by UK 14304, oxymetazoline and clonidine became more potent and efficacious at the Thr381Lys alpha2C AR, whereas the response as mediated by talipexole displayed a higher potency with an unaltered maximal response. Whereas only small differences in ligand's intrinsic activities between the wt alpha2A, alpha2B and alpha2C AR fusion proteins were observed with most ligands, oxymetazoline was virtually silent at the alpha2A AR while active as a partial and apparently full agonist at the alpha2C AR and alpha2B AR, respectively. The mutant alpha2 AR subtypes could be differentiated using the apparent positive efficacy of ligands that used to be defined as antagonists. The following rank order of maximal responses was observed for the Thr381Lys alpha2C AR: idazoxan approximately equals SKF 86466 > atipamezole >> dexefaroxan; Thr373Lys alpha2A AR: SKF 86466 > idazoxan = atipamezole > dexefaroxan; and Thr370Lys alpha2B AR: atipamezole > idazoxan dexefaroxan. RX 811059 (10 microM) was the only compound to be completely silent at both the wt and mutant alpha2 AR subtypes. In conclusion, silent alpha2 AR ligands are probably rare in these specified alpha2 AR systems. Most antagonists may actually possess partial agonist properties at the alpha2 AR subtypes, which are facilitated by the same mutation in the distal portion of their third intracellular loop.

Adrenergic Agonists↗
PubMed2002

Disparate binding of chaperone proteins by HLA-A subtypes.

We examined chaperone association with subtypes of HLA-A68 differing at positions 116 and/or 70, and analyzed the surface expression of each A68 subtype. Our findings with A68 indicate that certain subtypes have inefficient association with the assembly complex and correspondingly high surface expression, dependent on the character of position 116. Specifically, poor association of A68 subtypes with the transporter associated with antigen processing correlated with a comparatively high level of W6/32(+) forms at the cell surface. This observation suggests that intracellular retention is a dominant function of the assembly complex and that natural differences in assembly complex interaction may dictate the level of surface expression of MHC class I molecules. We also found that position 116 was crucial for HLA-A68 subtype association with the assembly complex. Our data contrast with results we obtained previously with HLA-B7 in that an aspartic acid at position 116 abrogated chaperone association for HLA-A68, whereas it increased association for HLA-B7. In total, HLA-A molecules exhibit natural allele-specific distinctions in chaperone association that correlate with differences in cell surface expression and with the identity of amino acid position 116.

Antiporters↗
PubMed1998

Somatostatin receptor subtypes, octreotide scintigraphy, and clinical response to octreotide treatment in patients with neuroendocrine tumors.

Several types of neuroendocrine tumor express high numbers of somatostatin receptors (sstr). We have compared the expression of sstr subtypes with the outcome of octreotide scintigraphy in patients with carcinoids and medullary thyroid carcinoma (MTC) in comparison with Hürthle cell tumors. The effect of sstr activation (octreotide treatment) on tumor markers was also studied in patients with disseminated carcinoid tumors. Six patients with carcinoid tumors (four midgut and two foregut), and three patients with thyroid tumors (one MTC, one Hürthle cell carcinoma, and one Hürthle cell adenoma) were studied. Octreotide scintigraphy visualized tumor sites in all nine patients. Macroscopic tumor was verified at these sites at subsequent surgical exploration. Using Northern blotting and subtype-specific riboprobes, sstr could be detected in all tumors examined. All five sstr subtypes were detected in most of the carcinoid tumors. All six carcinoids expressed sstr2. This was in contrast to the findings for the thyroid tumors analyzed, which also expressed several sstr subtypes but in some cases lacked expression of sstr2. This was also the case for normal thyroid tissue. Clinically, octreotide treatment of the patients with midgut carcinoid tumors resulted in palliation of hormonal symptoms accompanied by a significant reduction of urinary 5-HIAA levels (28-71%). These results indicate that carcinoid tumors frequently express all five sstr subtypes. The thyroid tumors also expressed multiple sstr but could lack expression of sstr2. Nevertheless, these tumors were visualized by octreotide scintigraphy, indicating that sstr2 expression is not a prerequisite for tumor imaging.

Adenocarcinoma↗
PubMed2002

Differential intracellular expression of CCR5 and chemokines in multiple sclerosis subtypes.

Chemokines are small chemoattractant cytokines which participate in the migration of immune cells into the CNS and contribute to the T cell-mediated pathogenesis of multiple sclerosis (MS). The expression of chemokines and their receptors in freshly isolated mononuclear cells from peripheral blood (PBMC) was studied in relation to MS subtype, disease duration and progression in a total of 57 patients with MS (22 relapsing remitting, RRMS; 21 secondary progressive, SPMS; 14 primary progressive, PPMS) and 17 healthy controls. The RNA expression of CCR5 in PBMC was analysed by reverse transcription polymerase chain reaction (RT-PCR) using specific oligonucleotide primers. The PBMC levels of CCR5-ligands MIP-1 alpha/beta and RANTES, and chemokines MCP-1, IL-8, lymphotactin, IP-10 and I-309 were analysed by ribonuclease protection assay (RPA). Significantly increased intracellular CCR5 RNA expression intensity was detected in PPMS when compared with SPMS ( p=0.009), RRMS ( p=0.013), and controls ( p=0.023). However, the surface expression of CCR5 on CD4(+) cells from PBMC, analysed by flow cytometry, appeared to be similar in all MS subtypes and controls. The CCR5-ligands RANTES and MIP-1b were expressed constitutively in all patients and controls. Interleukin-8 was found in all MS subtypes and controls, but IP-10 was detected only in RRMS and SPMS, and lymphotactin occasionally in other subtypes but PPMS. MCP-1, MIP-1a or I-309 were not expressed in any of the groups studied. A correlation was found between the RNA levels of RANTES and CCR5 in PPMS ( r=0.735). Differential profile in the expression of CCR5 and chemokines between PPMS and other MS subtypes may contribute to differences in the pathogenesis of MS and thus can be of importance in the development of new treatments for MS.

Adult↗
PubMed2006

Genetic clonality is a feature unifying nephroblastomas regardless of the variety of morphological subtypes.

Nephroblastomas are embryonal tumors exhibiting a wide variety of different morphological features and genetic changes. Some of the genetic aberrations were associated with a certain histological subtype. It is generally assumed that nephroblastomas develop as subclonal proliferations from nephrogenic rests. However, so far, a very limited amount of tumors from only part of the morphological spectrum of nephroblastomas was investigated. We therefore investigated the clonality of 45 tumors of all different histological subtypes. The number of each subtype was in accordance with the percentage of occurrence of the respective subtype. We analyzed a highly polymorphic locus of the human androgen receptor gene for nonrandom X-inactivation of genomic DNA using a methylation-sensitive restriction enzyme. Data were obtained for 39 tumors. Eighteen of the tumors included were noninformative in the genetic locus examined, the remaining 21 tumors were monoclonal regardless of the histological subtype. Our findings therefore support the hypothesis that Wilms' tumors are monoclonal proliferations despite their large variety of morphological features.

Humans↗
PubMed2005

Expression and localization of muscarinic acetylcholine receptor subtypes in rat efferent ductules and epididymis.

The expression of muscarinic acetylcholine receptor (mAChR) subtypes (M(1)-M(5)) was studied in the rat efferent ductules and epididymis at the mRNA and protein levels. The relative abundance of each mAChR transcript subtype differed depending on the tissue and the epididymal region analyzed. The M(1) mAChR mRNA level was more abundant in the efferent ductules than in the caput and cauda of the epididymis. The M(2) mAChR mRNA level was similar between the efferent ductules and caput of the epididymis and higher in the cauda region. The M(3) mAChR mRNA level was low in the efferent ductules and caput of the epididymis, but high levels were detected in the cauda region. mRNAs for M(4) and M(5) mAChRs were not detected in these tissues. Our studies indicated a variable degree of immunostaining for each mAChR subtype in a cell-type and tissue-specific pattern. M(1) mAChR was detected over the efferent ductule epithelium. M(2) and M(3) mAChRs were observed in the apical region of the ciliated cells. Apical and narrow cells of the initial segment showed distinct staining by M(1) antibody, whereas a supranuclear reaction was noted in the principal cells of the caput of the epididymis. In addition, staining for M(1) and M(2) mAChRs was visible in the apical membrane of some epithelial cells of the cauda region. M(3) mAChR was detected in the peritubular smooth muscle of the efferent ductules and epididymis. Functional studies suggested the involvement of this subtype in epididymal tubule contraction. Thus, the cell-specific expression of the various mAChR subtypes in the efferent ductules and epididymis suggests that these receptors play a role in the modulation of luminal fluid composition and smooth muscle contraction.

Animals↗
PubMed2002

Prevalence of swine influenza virus subtypes on swine farms in the United States.

Serologic and virologic prevalence of infection with different swine influenza virus (SIV) subtypes was investigated using swine sera, nasal swabs and lung samples that had been submitted for a diagnosis to the Minnesota Veterinary Diagnostic Laboratory. A total of 111,418 pig sera were tested for SIV antibody between 1998 and 2000, and 25,348 sera (22.8%) were found to be positive by the hemagglutination inhibition (HI) test. Of the positive samples, 16,807 (66.7%) and 8,541 (33.7%) had antibody to H1 and H3 subtypes, respectively. Between January 1998 and May of 2001, a total of 3,561 nasal swabs or lung samples were examined for the presence of SIV, and SIV was isolated from 1,124 samples (31.7%). Of these isolates, 869 (77.3%) and 255 (22.7%) were subtyped as H1 and H3, respectively, by the HI method. For further characterization, 120 SIV isolates each from 1998 to 2001 were randomly selected from a culture collection and their hemagglutinin (HA) and neuraminidase genes examined by reverse transcription-PCR and sequencing. Of the 480 isolates, 322 (67.1%), 22 (4.6%) and 129 (26.9%) were subtyped as H1N1, H1N2 and H3N2, respectively. The remaining 7 samples (1.5%) were found to contain both H1N1 and H3N2 viruses. The SIV H1N2 subtype was isolated from 1, 8, and 13 samples in 1999, 2000, and 2001, respectively. The 22 H1N2 isolates originated from 9 different states of the United States. Genetic screening of the HA genes of 12 selected H1N2 isolates showed that 8 of them had a close phylogenetic relationship with the Indiana isolate of H1N2 (A/Swine/Indiana/9K035/99), while 4 isolates were closely related to classical SIV H1N1.

Amino Acid Sequence↗
PubMed2002

Infection of macaques with chimeric simian and human immunodeficiency viruses containing Env from subtype F.

Chimeric simian and human immunodeficiency viruses (SHIVs) are useful for investigating the pathogenicity of human immunodeficiency virus (HIV-1) and to develop an anti-HIV-1 vaccine. We attempted to construct SHIVs containing Env from various subtypes, because almost all SHIVs which have been reported so far have Env from HIV-1 that belongs to subtype B. Two infectious SHIVs containing Env from two strains of HIV-1, CMR304 and CMR306, which belong to subtype F and A, respectively, were newly obtained. These SHIVs essentially showed a coreceptor usage and a neutralization pattern that were similar to those of the parental HIV-1s. In macaque PBMC, SHIVcmr304 replicated with kinetics similar to that of prototypic SHIV-NM-3rN with HIV-1 NL432 Env, but SHIVcmr306 replicated poorly. Inoculation of four rhesus macaques with SHIVcmr304 resulted in an increase of plasma viral load in all the macaques, though viral RNA copies were 100-fold lower than that in the infection with NM-3rN. This SHIV containing Env from HIV-1 subtype F will be a valuable source for the analysis of HIV-1 subtype F and the evaluation of vaccine candidates as a genetically divergent challenge virus.

Animals↗
PubMed2003

Phylogenetic analysis of Vietnamese isolates of feline immunodeficiency virus: genetic diversity of subtype C.

Phylogenetic relationships of novel Vietnamese strains of feline immunodeficiency virus (FIV) were analysed. One Vietnamese strain was found to cluster with subtype D, which was previously known only in Japan, while the other seven strains were placed with members of subtype C. Calculation of the relative numbers of mutations resulting in amino acid and silent changes in FIV env subtypes suggested that subtype C isolates may be less structurally constrained (potentially more pathogenic) than subtype B.

Animals↗
PubMed1999

Comparison of three different commercial methods for measuring plasma viraemia in patients infected with non-B HIV-1 subtypes.

In order to determine whether commercial assays presently in use for the quantification of plasma human immunodeficiency virus type 1 (HIV-1) RNA levels detect different genetic viral subtypes with the same reliability, a panel of 38 samples corresponding to 22 HIV-1-infected patients, representing non-B subtypes A-F, was examined. One to three plasma samples belonging to each individual were tested by the second-generation HIV-1 branched DNA (bDNA) assay (Chiron, Spain), the Nuclisens assay (Organon-Teknika, Spain), the Amplicor Monitor reverse transcriptase polymerase chain reaction assay (Roche, Spain), and the Ultradirect Monitor (Roche) using primers specifically designed to amplify non-B HIV-1 subtypes. Each of the different methods for measuring viral load showed a distinct sensitivity for non-B HIV-1 subtypes. Values higher than the assay detection limit were obtained in 22 (57.9%), 33 (86.8%), and 37 (93.3%) samples using the bDNA, Nuclisens, and Monitor assays, respectively. Significantly different values (>0.5 logs) were found in 55.3%, 81.6%, and 71.1% of specimens comparing results provided by bDNA and Nuclisens, bDNA and Monitor, and Nuclisens and Monitor, respectively. Quantitative values provided by the Ultradirect Monitor test using non-B primers were particularly discordant with the other tests. Overall, 44.7% of samples yielded higher viral load values with this assay than with the regular Monitor assay, reflecting its enhanced sensitivity for non-B subtypes; however, the reproducibility of this test was low. These results support the recommendation of always using the same assay when monitoring plasma viraemia.

HIV Infections↗
PubMed2005

Different risk factor profiles between subtypes of ischemic stroke. A case-control study in Korean men.

Ischemic stroke is composed of subtypes with variable underlying pathogenesis and studies on ischemic stroke as a whole may inadequately evaluate risk factors, being influenced by subtype distribution among studied population. This study aimed to evaluate risk factors associated with individual ischemic stroke subtypes defined by the Trial of ORG10172 in Acute Stroke Treatment. In a case-control study (290 first-ever ischemic stroke cases and 1160 individually matched controls without stroke) nested within Korean male public servants cohort, a range of potential risk factors measured at periodic health surveys prior to the onset of stroke event were examined using conditional logistic regression analysis. Increased risk for large-artery atherosclerosis was associated with hypercholesterolemia (> or = 6.2 mmol/L), hypertension, and smoking. Increased risk for small-artery occlusion was associated with hypertension, hyperglycemia (> or = 7.0 mmol/L), and frequent alcohol intake. No specific risk factor was identified for cardioembolism. For combined ischemic stroke, hypercholesterolemia, hyperglycemia, hypertension, and smoking were associated with the increased risk, but the relative odds were much smaller than those estimated from subtype analysis. Significance of risk factors evaluated for subtypes, rather than ischemic stroke as a whole, should be reflected in preventive efforts against the burden of ischemic stroke.

Adult↗
PubMed2006

Pharmacokinetic/pharmacodynamic modeling of total lymphocytes and selected subtypes after oral budesonide.

In the present pharmacokinetic/pharmacodynamic (PK/PD) evaluation, cortisol, total lymphocytes, and lymphocyte subpopulations were monitored following single oral doses of two oral formulations of 3 mg budesonide (BUD) (Dosage Forms A and B) in order to assess the differential effects that BUD may have on cortisol suppression and the modulation of blood lymphocyte subtypes. On a single occasion, five subjects received one 3 mg capsule of Dosage Form A, four received three capsules of Dosage Form A (single dose of 9 mg), and five received three capsules of Dosage Form B (single dose of 9 mg). Placebo capsules were administered to six subjects in the study. Cortisol concentrations, total lymphocyte counts, and lymphocyte subpopulation counts for the CD3, CD4, CD8, CD19, and CD56/16 were fitted to an in direct PK/PD response model that described the effects of BUD on serum cortisol concentrations as well as the combined effects of BUD and cortisol on total lymphocytes and the CD3, CD4, CD8, CD19, and CD56/16 subtypes. Data were also analyzed using noncompartmental methods. The PK/PD model fitted the data with the exception of data for CD56/16. The IC(50) value for unbound BUD acting on total lymphocytes was 0.276 ng/ml while the IC(50) values for unbound BUD acting on lymphocyte subtypes ranged from 0.150 ng/ml for CD4 to 0.364 ng/ml for CD8. The IC(50) values for the effects of BUD on serum cortisol were lower (0.079 ng/ml). The results of PK/PD modeling and noncompartmental analysis indicate that BUD has a smaller effect on the CD8 subtype and larger effects on the CD4 and CD19 subtypes, relative to the effect on total lymphocytes, and that cortisol suppression, although not a direct immunological biomarker, may be a more sensitive marker for the systemic effect of corticosteroids.

Administration, Oral↗
PubMed2003

Immunohistochemical detection of somatostatin receptor subtypes in "clinically nonfunctioning" pituitary adenomas.

Pituitary tumors diagnosed before surgery as "non-functioning" in fact represent a heterogenous group, the majority of which express glycoprotein hormones or their free subunits. It is known that some of them expresses somatostatin receptors, but the data available until now rarely refer to the receptor subtype. Five different subtypes of somatostatin receptors (sst1-5) have been cloned. We studied 18 pituitary tumors diagnosed before surgery as "non-functioning." After the surgery the tumors were immunostained with antibodies against pituitary hormones and alpha subunit as well as with antibodies against the somatostatin receptor proteins 1-5. Thirteen adenomas expressed immunoreactivity for FSH, LH, and/or alpha subunit and were classified as gonadotroph adenomas. The remaining five adenomas were immunonegative for all the examined pituitary hormones and were diagnosed as null cell adenomas. All the adenomas of both the groups showed immunopositivity for at least three receptor subtypes. The strongest immunopositivity was found in both groups with anti-sst1 and anti-sst5 antibodies. The marked immunopositivity was also revealed in both groups with anti-sst2B antibody. On the other hand, the sst2A immunopositivity was weak or absent in a majority of tumors. The main difference between two groups was in the sst4 receptor subtype which was absent in all but two gonadotroph adenomas but present in all but one null cell adenoma. These findings suggest that "non-functioning" pituitary adenomas are potential candidates for therapy with somatostatin analogs targeted mainly to the receptor subtypes 1 and 5.

Adenoma↗
PubMed2026

Unveiling novel transcriptomic prognostic biomarkers for specific breast cancer subtypes and treatment regimens.

BACKGROUND: Breast cancer (BRCA) is the most common cancer in women worldwide, yet current gene expression panels offer limited insight into treatment responses across different subtypes and therapies. This study aimed to identify reliable biomarkers for predicting treatment outcomes in specific BRCA subtypes and treatment regimens. METHODS: This study analyzed transcriptomic data from The Cancer Genome Atlas to identify differentially expressed genes (DEGs) in patient groups treated with different combinations of hormone therapy (H), chemotherapy (C), radiotherapy (R), and targeted therapy (T). Non-negative matrix factorization clustering was performed to stratify patients into clusters representing different BRCA subtypes. Functional enrichment analysis was performed, and survival assessments were conducted using the METABRIC dataset. RESULTS: A total of 1,148 DEGs were identified across treatment regimens, with 75 common DEGs shared across multiple regimens. Among these, 12 candidate biomarkers were associated with luminal subtypes treated with H, including LRP1B, of which high expression predicted cancer recurrence. In triple-negative breast cancer (TNBC) treated with C, 76 candidate biomarkers were identified, including TTYH1 for recurrence and ANXA8L1 and MPZ for non-recurrence. Functional analyses identified intermediate filament organization and keratinization as pathways associated with specific candidate biomarkers of TNBC following C. Survival analysis using METABRIC strengthened the prognostic ability of LRP1B and TTYH1 to predict worse survival and ANXA8L1 and MPZ to predict prolonged survival, with four additional prognostic biomarkers. CONCLUSION: This study identified gene expression prognostic biomarkers for luminal and TNBC subtypes, thereby supporting personalized therapies. Further experimental validation is required to confirm these findings for clinical application. CLINICAL TRIAL REGISTRY: No.

Breast cancer↗
PubMed1991

Allosteric regulation of cloned m1-m5 muscarinic receptor subtypes.

Allosteric regulation of [3H]N-methylscopolamine [( 3H]NMS) and [3H]quinuclidinyl benzilate [( 3H]QNB) dissociation from the m1-m5 muscarinic receptor subtypes was examined in transfected CHO-K1 cells. Half-times of dissociation of [3H]NMS from cell membranes (at 23 degrees) ranged from less than 5 min for the m2 subtype to more than 60 min for the m5 subtype. For [3H]QNB, half-times (at 37 degrees) ranged from 1 hr (m2) to almost 4 hr (m3). The presence of gallamine slowed the dissociation of [3H]NMS from all of the subtypes, with an order of potency of m2 greater than m4 greater than m1 greater than m3 greater than m5. Dissociation of [3H]QNB from m1 and m2 receptors was modulated by gallamine in the biphasic manner that we have described previously for cardiac receptors; that is, low concentrations (1-10 microM) of gallamine accelerated dissociation, while 1 mM gallamine slowed it. Verapamil slowed the dissociation of [3H]-QNB from the m2 receptor in a monophasic manner, while the action of d-tubocurarine was qualitatively similar to that of gallamine. The potency of gallamine in allosterically regulating the m2 receptor was inversely related to ionic strength. Inactivation of pertussis toxin-sensitive G proteins abolished the ability of guanine nucleotides to regulate agonist affinity at the m2 receptor, but had no effect on allosteric regulation of the m2 receptor. These findings indicate that susceptibility to allosteric regulation varies in a complex way across muscarinic receptor subtypes and according to the choice of ligand.

Animals↗
PubMed1992

Angiotensin II binding sites in the hamster brain: localization and subtype distribution.

This study was designed to characterize the distribution of angiotensin II (AII) binding sites in the hamster brain. Brain sections were incubated with [125I][sar1,ile8]-angiotensin II in the absence and presence of angiotensin II receptor subtype selective compounds, losartan (AT1 subtype) and PD123177 (AT2 subtype). Binding was quantified by densitometric analysis of autoradiograms and localized by comparison with adjacent thionein stained sections. The distribution of AII binding sites was similar to that found in the rat, with some exceptions. [125I][sar1,ile8]-angiotensin II binding was not evident in the subthalamic nucleus and thalamic regions, inferior olive, suprachiasmatic nucleus, and piriform cortex of the hamster, regions of prominent binding in the rat brain. However, intense binding was observed in the interpeduncular nucleus and the medial habenula of the hamster, nuclei void of binding in the rat brain. Competition with receptor subtype selective compounds revealed a similar AII receptor subtype profile in brain regions where binding is evident in both species. One notable exception is the medial geniculate nucleus, predominately AT1 binding sites in the hamster but AT2 in the rat. Generally, the AII binding site distribution in the hamster brain parallels that of the other species studied, particularly in brain regions associated with cardiovascular and dipsogenic functions. Functional correlates for AII binding sites have not been elucidated in the majority of brain regions and species mismatches might provide clues in this regard.

Angiotensin II↗
PubMed1994

Dopamine receptor distribution in the rat CNS: elucidation using anti-peptide antisera directed against D1A and D3 subtypes.

Anti-peptide antibodies were generated against amino acid sequences of intracellular and extracellular portions of the native proteins for the cloned rat D1A and D3 dopamine receptor subtypes in order to determine the cellular distribution of these specific forms in the brain. These polyclonal antisera exhibited high specific titers, assessed by ELISA and immunofluorescent detection of functional recombinant receptor proteins expressed in stably transfected Chinese hamster ovary (CHO) cells. Central nervous system (CNS) areas of the male rat were examined using standard immunofluorescent methods in fresh frozen tissues. This paradigm detected D1A-like and D3-like dopamine receptor staining primarily in larger-sized neurons throughout layers 3 and 5 of the cortex, in medium-diameter somata of the striatum, and in the densely packed cells of the olfactory tubercle and hippocampal formation. More attenuated immunoreactivity for both dopamine receptor subtypes was noted in the substantia nigra, not associated with perikarya. Differences in cellular staining patterns and intensity were evident between the D1A-like and D3-like dopamine receptor subtypes. Equivalent morphological elements exhibited dopamine receptor expression following incubation using antisera generated against either extracellular or intracellular epitopes of either the D1A or D3 native proteins. Dopamine receptor immunoreactivity could not be detected in the cerebellum at equivalent antisera dilutions used to discriminate cellular staining patterns within the forebrain. Fluorescent-labeled latex microspheres were infused into the substantia nigra terminal fields to retrogradely identify the cell bodies of the striatonigral projection system. This paradigm showed that 80% of striatonigral neurons expressed D1A-like receptors, while 65% demonstrated D3-like dopamine receptor staining. This distribution for the D1A-like and D3-like receptor subtypes suggests that overlap may occur in the expression of the receptors in the striatonigral neuron population. Our previous results localizing cellular D2-like receptor expression patterns in this projection system of the rat neostriatum implies that all three of these dopamine receptor subtypes may be co-expressed in this efferent system.

Amino Acid Sequence↗