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PubMed1989

Preliminary biochemical characterization of two angiotensin II receptor subtypes.

Two angiotensin II receptor subtypes (A and B) are described from rat and human tissues. They have been characterised using specific peptidic and non-peptidic ligands with affinities differing by 1000 fold or more. These subtypes are present in adrenal glomerulosa of both species. Human uterus contains only subtype A, whereas both subtypes are found in rat uterus. Vascular smooth muscle cells in culture express only subtype B. Dithio-threitol totally inhibits binding to subtype B, but enhances the affinity to subtype A. There is a good correlation between the affinities of the selected agonists and antagonists for the two subtypes in the various tissues tested which is a usual requirement for receptor classification.

Adrenal Glands↗
PubMed1990

Molecular characterization of a new hemagglutinin, subtype H14, of influenza A virus.

Two influenza A viruses whose hemagglutinin (HA) did not react with any of the reference antisera for the 13 recognized HA subtypes were isolated from mallard ducks in the USSR. Antigenic analysis by hemagglutination inhibition and double immunodiffusion tests showed that the HAs of these viruses are similar to each other but distinct from the HAs of other influenza A viruses. Nucleotide sequence analysis showed that these HA genes differ from each other by only 21 nucleotides. However, they differ from all other HA subtypes at the amino acid level by at least 31% in HAI. Thus, we propose that the HAs of these viruses [A/Mallard/Gurjev/263/82 (H14N5) and A/Mallard/Gurjev/244/82 (H14N6) belong to a previously unrecognized subtype, and are designated H14. Unlike any other HAs of influenza viruses, the H14 HAs contained lysine at the cleavage site between HA1 and HA2 instead of arginine. Experimental infection of domestic poultry and ferrets with A/Mallard/Gurjev/263/82 (H14N5) showed that the virus is avirulent for these animals. Based on comparative sequence analysis of different HA genes, it is suggested that differences of 30% or more at the amino acid level in HA1 constitute separate subtypes. Phylogenetic analysis of representatives of each HA subtype showed that H14 is one of the most recently diverged lineages while H8 and H12 branched off early during the evolution of the HA subtypes. These latter two subtypes (H8 and H12) have been isolated very infrequently in recent years, suggesting that these old subtypes may be disappearing from the influenza reservoirs in nature.

Amino Acid Sequence↗
PubMed1989

Endometrial adenocarcinoma histologic subtypes: clinical and pathologic profile.

All cases of endometrial adenocarcinoma treated at the Geisinger Medical Center from January 1970 to June 1980 were retrospectively reviewed in an attempt to elucidate the clinical and pathologic profiles of the various histologic subtypes. Complete clinical and pathologic data was available in 418 cases of stage I endometrial adenocarcinoma. The frequency of the histologic subtypes were adenocarcinoma 66%, adenoacanthoma 16%, adenosquamous 5%, papillary 8%, clear cell 3%, and secretory 2%. Absolute 5-year survival was adenocarcinoma 88%, adenoacanthoma 91%, adenosquamous 62%, papillary 63% (P less than 0.01), clear cell 43% (P less than 0.001), and secretory 89%. When comparing the clinical and pathologic profile of the various histologic subtypes, adenosquamous (52%, P less than 0.001) and clear cell (43%, P less than 0.05) were associated with the highest percentage of grade 3 differentiation. Adenosquamous (38%, P less than 0.05) and clear cell (36%) also had the highest percentage of deep myometrial invasion. Papillary subtype (46%, P less than 0.05) was associated with the highest percentage of nulliparity. There was no difference among the subtypes when comparing menopausal status, exogenous estrogen, obesity, hypertension, diabetes, or uterine size. In summary, (1) adenocarcinoma and adenoacanthoma are the most frequent subtypes; (2) adenosquamous, papillary, and clear cell have decreased 5-year survival; (3) the decreased 5-year survival in adenosquamous and clear cell subtypes appears to be associated with increased grade 3 differentiation and deep myometrial invasion while the poor prognosis associated with papillary subtype was not related to grade or myometrial invasion.

Adenocarcinoma↗
PubMed1985

Enzyme immunoassay, complement fixation and hemagglutination inhibition tests in the diagnosis of influenza A and B virus infections. Purified hemagglutinin in subtype-specific diagnosis.

The efficacy of enzyme immunoassay (EIA) in detecting diagnostic antibody rises to influenza A and B viruses was compared with complement fixation (CF) and hemagglutination inhibition (HI) tests in 455 patients with an acute respiratory infection. EIA and HI detected significantly more diagnostic antibody rises against influenza A than the CF method (96 and 87 vs. 47, respectively). In the case of influenza B significantly more diagnostic influenza B antibody rises were observed by EIA than by CF or HI (59 vs. 37 and 40, respectively). In most of the cases antibody rises in EIA were found in both IgG and IgA isotypes whereas increases in IgM antibodies were seen less frequently. Purified hemagglutinins (HA) were prepared from influenza A HI- and H3-subtypes and from influenza B viruses and used as antigens in EIA and the results were compared with those of HI. Infections caused by influenza A HI-subtype showed good homologous antibody responses in EIA but heterologous antibody responses to H3-subtype and influenza B HAs were frequently observed. Heterologous responses were clearly less frequent in patients with infections caused by the H3-subtype. Influenza B infections occasionally raised HA antibodies against influenza A H1-subtype but not to the H3-subtype. Interestingly, HI detected these heterologous responses at least as frequently as EIA. When whole viruses were used as antigens in EIA, subtype specificity was not observed and cross-reactions between influenza A and B virus antibodies were found. These observations suggest that, although EIA can show greater diagnostic efficacy over HI and CF methods, HI is still the serological method of choice in determining the causative subtype of influenza A virus infection.

Adolescent↗
PubMed1992

Differential expression of two alpha 2-adrenergic receptor subtype mRNAs in human tissues.

Genetic subtypes of alpha 2-adrenergic receptors (AR) may mediate distinct physiological functions, and undergo differential cell type-specific regulation. Thus, these distinct receptor subtypes are possible targets for the development of subtype-selective drugs. We have analyzed the tissue distribution of two human alpha 2-adrenoceptor subtype gene mRNAs, alpha 2-C4 and alpha 2-C10, in normal human fetal and adult tissues. Both receptor subtype mRNAs were abundantly expressed in fetal brain and choroid plexus. In non-neural fetal tissues, alpha 2-C10 mRNA was detected in spleen, kidney, adrenal gland, and skin, while alpha 2-C4 transcripts were observed only in kidney and skin. Most regions of the adult brain also expressed both subtypes, but with marked quantitative differences. For example, cerebral cortex contained predominantly alpha 2-C10 mRNA, whereas the caudate nucleus expressed mostly alpha 2-C4 mRNA. In adult peripheral tissues, alpha 2-C10 mRNA expression was most abundant in spleen and renal cortex, and expression of alpha 2-C4 mRNA was strongest in renal cortex and medulla. These different expression patterns provide evidence for the differential regulation of the two alpha 2-adrenergic receptor genes and warrant further investigation with techniques capable of improved anatomical resolution. Regional differences in receptor subtype expression may be valuable for the development of new, subtype-selective pharmacological agents with more targeted actions compared to currently used alpha 2-adrenoceptor agonists and antagonists.

Animals↗
PubMed1986

An improved biochemical method for the analysis of HLA-class I antigens. Definition of new HLA-class I subtypes.

A simple method is described for the biochemical analysis of HLA class I antigens. It is a modification of a previously published procedure for one-dimensional isoelectric focusing (1D-IEF), giving improved resolution and offering larger sample capacity. One million viable cells suffice for analysis, and no more than 25 muCi of radioisotope (35S-methionine) are required. The usefulness of the method is illustrated by the characterization of a total of four biochemically distinct subtypes of HLA-B27, three subtypes of HLA-A24, two subtypes of HLA-A11, three subtypes of HLA-A2, two subtypes of HLA-Bw60, two subtypes of HLA-Bw62, and four subtypes of HLA-B35 in a panel of 24 cells selected for the expression of HLA-B27. We envision that this technique will allow a rigorous classification of HLA-A,B antigens into novel subtypes. Populations of distinct ethnic origin are especially of interest in this regard. This technique might also be used as an additional criterion for the official classification of HLA-A,B antigens.

HLA Antigens↗
PubMed1989

The BF F subtypes are detectable in the Ba fragment of factor B.

The unanimous recognition of the two subtypes FA and FB of the BF*F allele has repeatedly been challenged. In the present investigation we are reporting about the unequivocal and simple detection of the subtypes on the Ba fragment of factor B by immunofixation isoelectric focusing after conversion with inulin. The common BF phenotypes F, S, and FS could be diagnosed in addition to the subtypes of BF*F which were observed in two regions acidic of the F major band. By comparison of standard phenotypes the subtypes in the Ba fragment corresponded to those of native factor B. All BF bands could be attributed to the Ba fragment by developing Western Blots with monoclonal antibodies directed against Ba. The distribution of the major BF phenotypes and alleles and the BF F subtypes in a population sample of 527 unrelated individuals from F.R.G. was in Hardy-Weinberg equilibrium. The allele frequency was determined to be 0.0731 for BF*FA, and 0.1053 for BF*FB. The advantages of determining the subtypes on the Ba fragment are: broadening of the FA/FB corridor, a more reliable diagnosis of phenotypes, improved distinction between homozygous FA and heterozygous FAFB types, and recognition of common BF phenotypes as well as subtypes in aged sera. It is suggested that the problem in the designation of BF F subtypes by different groups should be resolved by an international reference typing.

Alleles↗
PubMed2005

Quantitative detection and differentiation of human herpesvirus 6 subtypes in bone marrow transplant patients by using a single real-time polymerase chain reaction assay.

Human herpesvirus (HHV)--6 infections are ubiquitous, but infection or reactivation under immunocompromised conditions, such as bone marrow or solid organ transplantation, can often result in serious clinical manifestations. Two HHV-6 subtypes are known. Most primary HHV-6 infections are caused by subtype 6B, but little information is available about the prevalence, distribution, and clinical divergence of 6A and 6B. To study this, we have developed a highly sensitive and specific real-time polymerase chain reaction (PCR) assay that can detect, quantitate, and reliably differentiate HHV-6A and -6B in clinical specimens. Exploiting a single-base variation in the DNA polymerase gene of these respective subtypes, we used melting curve analysis for subtype discrimination. Moreover, this assay's ability to discriminate HHV-6 subtypes was confirmed by PCR/restriction fragment length polymorphism analysis of the HHV-6 large tegument protein gene and PCR amplicon size-discrimination analysis of the HHV-6 immediate-early gene. Using this assay, we present our findings about the prevalence and distribution of these subtypes in bone marrow transplant patients. Of 803 plasma specimens tested from 353 patients, 136 specimens (17%) from 60 patients were determined to be HHV-6 positive. We analyzed these HHV-6--positive patients for subtype identification by using our newly developed assay and determined that 58 patients (97%) were HHV-6B positive and 2 patients (3%) were HHV-6A positive. No patient was coinfected with both subtypes. This assay can be a sensitive, genotype-specific, rapid method to reliably diagnose life-threatening HHV-6 infections in immunocompromised patients and can be useful in guiding and monitoring specific therapy.

Bone Marrow Transplantation↗
PubMed2006

Prenatal smoking exposure and dopaminergic genotypes interact to cause a severe ADHD subtype.

BACKGROUND: In utero exposure to smoking and alcohol are common risk factors that have been associated with attention-deficit/hyperactivity disorder (ADHD) in human beings and animal models. Furthermore, molecular studies have focused on the association between ADHD and DNA polymorphisms in dopamine pathway-related genes. We examined the joint effects of genetic and prenatal substance exposures on DSM-IV and population-defined subtypes of ADHD. METHODS: Logistic regression was used to assess the relationship between ADHD subtypes, DAT1 and DRD4 polymorphisms, and prenatal substance exposures in a birth-record sample of male and female twin pairs, aged 7-19 years. RESULTS: Interactions between prenatal exposure to smoking and variations in the DAT1 and DRD4 loci were observed in children with either the DSM-IV or population-defined ADHD combined subtypes. The odds of a diagnosis of DSM-IV combined subtype was 2.9 times greater in twins who had inherited the DAT1 440 allele and who were exposed, than in unexposed twins without the risk allele. The OR was 2.6 in the population-defined subtype. Odds ratios for the DRD4 seven-repeat allele were 3.0 (2.8) in the population-defined (DSM-IV) combined ADHD subtypes. The OR for exposed children with both alleles was 9.0 (95% confidence interval=2.0-41.5) for the population-defined combined subtypes. CONCLUSIONS: Results indicate that smoking during pregnancy is associated with specific subtypes of ADHD in genetically susceptible children.

Adolescent↗
PubMed2004

A critical evaluation of obsessive-compulsive disorder subtypes: symptoms versus mechanisms.

Recently, experts have suggested that obsessive-compulsive disorder (OCD), a highly heterogeneous condition, is actually composed of distinct subtypes. Research to identify specific subtypes of OCD has focused primarily on symptom presentation. Subtype models have been proposed using factor analyses that yield dimensional systems of symptom categories, but not necessarily distinct subtypes. Other empirical work has considered the role of neuropsychological functioning and comorbidity as part of a comprehensive scheme for subtyping OCD. The identified dimensions from all of these studies have implications for the treatment of OCD. In this article, we review the research on subtypes of OCD, focusing on subtype schemes based upon overt symptom presentation and neuropsychological profiles. We also review research pertinent to alternative subtyping schemes, both conceptually and methodologically. The research is critically examined and implications for treatment are discussed. Recommendations for future investigations are offered.

Diagnosis, Differential↗
PubMed2005

Electro-clinical and imaging characteristics of focal cortical dysplasia: correlation with pathological subtypes.

INTRODUCTION: Focal cortical dysplasia (CD) is a common cause of pharmaco-resistant epilepsy. CD is due to abnormalities in neuronal migration, proliferation, and/or differentiation that result in four distinct pathological subtypes: 1A, 1B, 2A, and 2B. In order to provide clinical correlation to these pathological subtypes, we reviewed the electro-clinical and imaging characteristics and surgical outcomes of the four pathological subtypes of CD. METHODS: We retrospectively reviewed patient data from epilepsy surgeries at the Cleveland Clinic Foundation between 1990 and 2002. Only those patients with the definite pathological diagnosis of isolated cortical dysplasia were included in the study (n = 145). RESULTS: Pathological subtypes 2A and 2B were predominantly frontal in location, and had a more severe epilepsy syndrome with lower intelligence quotient scores than subtypes 1A and 1B. Patients with subtype 1A FCD had less severe, later onset epilepsy that was predominantly located in the temporal lobe. Risk factors for epilepsy included febrile seizures for type 1A, head trauma for types 1A and 1B, and perinatal adverse events for type 2B. Type 2B demonstrated significantly more FLAIR signal abnormalities than the other groups. Sixty-three percent of patients overall had an Engel I outcome at 6 months follow-up. The best outcomes were in the 2B subtype, and in those who did not require an invasive EEG evaluation. CONCLUSIONS: Clinically important differences exist between the pathological subtypes of CD, which may assist in their management, and provide further insight into their underlying pathophysiology.

Adolescent↗
PubMed2005

Clinical utility of genotyping resistance test on determining the mutation patterns in HIV-1 CRF01_AE and subtype B patients receiving antiretroviral therapy in Hong Kong.

BACKGROUND: HIV-1 genotypic resistance test (GRT) has been widely used to monitor HIV infection but only few reports revealed the mutation patterns of non-B HIV-1 subtypes. OBJECTIVE: To evaluate the concordance of GRT and clinical treatment outcomes on different HIV-1 subtypes and monitor the mutation patterns and frequencies. STUDY DESIGN: Pre- and post-treatment plasma samples from 123 patients (39 treatment naïve and 84 treatment experienced) were tested by ViroSeq HIV-1 Genotyping System followed by analysis using the Stanford HIV database. The mutation patterns and frequencies developed in the pol gene were compared among subtypes. RESULTS: HIV-1 subtypes among patients in Hong Kong were mainly subtype B and CRF01_AE. Primary mutation was not detected among all pre-treatment samples. For post-treatment samples, primary mutations were only detected in the treatment failure group. The mutation patterns and frequencies were similar between CRF01_AE and subtype B viruses. However, the frequencies of L74V/I and K103N in the reverse transcriptase region were different between CRF01_AE and subtype B viruses. VirtualPhenotype was unable to analyze an in-frame insertion of arginine and isoleucine at protease codon 35 of one CRF01_AE isolate. CONCLUSIONS: This is the first report to demonstrate the high degree of concordance of longitudinal genotyping data and clinical treatment outcome in patients harboring different HIV-1 subtypes. Our findings shed light to the emergence of resistance mutations and its testing in CRF01_AE, which is relevant to other prevailing places in Asia.

Algorithms↗
PubMed2006

Cytomegalovirus and Epstein-Barr virus subtypes--the search for clinical significance.

Cytomegalovirus (CMV) as well as Epstein Barr virus (EBV) genomes include regions which show in part substantial polymorphisms. Characterization of several polymorphic regions led to the identification of various CMV and EBV subtypes. Within the last years there have been undertaken numerous efforts to find out whether the diverse subtypes differentially contribute to clinical manifestations. However, although some associations have been described so far between a certain virus subtype and the development of individual diseases these analyses were greatly complicated by the huge genomic background of CMV and EBV, by the large variety of individual host-virus relations and by differences in the geographic or demographic subtype distribution. In addition, it was shown meanwhile that a substantial proportion of virus infections is due to mixed infections with different subtypes. In this review we will give an overview of the current knowledge concerning the clinical significance of individual CMV and EBV subtypes, defined by characterization of selected polymorphisms. In addition, we also focus on recent analyses which show that infection with mixed virus subtype populations may be disadvantageous compared to single virus subtype infections.

Cytomegalovirus↗
PubMed2005

Evaluation of an oligonucleotide ligation assay for detection of mutations in HIV-1 subtype C individuals who have high level resistance to nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors.

The oligonucleotide ligation assay (OLA) has been proposed as an affordable alternative to sequence-based HIV-1 drug resistance testing in resource poor settings. The aim was to evaluate OLA for detecting mutations K103N, Y181C, K65R, Q151M, M184V and T215Y/F in subtype C. Forty-four subtype C and 8 subtype B HIV-1 positive individuals were analysed using the ViroSeqtrade mark HIV-1 genotyping assay (Applied Biosystems, Foster City, CA). A one-step RT-PCR and nested PCR were performed using subtype B specific primers from the OLA kit (NIH AIDS Research and Reference Reagent Program). Seventy-eight subtype C sequences were used to design subtype C specific primers. Ligation and detection steps were followed according to OLA kit protocol. For codons, K103N, Y181C, K65R, Q151M, M184V and T215Y/F, four or more mismatches compared to the probe or mismatches less than four bases from the ligation site were not tolerated. Results revealed accurate identification of mutations in 2/10, 4/9 3/9, 6/7, 2/7 and 6/7 VQA samples and 5/20, 4/17 0/20, 18/24, 5/24 and 13/24 subtype C positive individuals, respectively. It was concluded that the probes and primers in the NIH reference kit would need modification to optimize detection of mutations in subtype C individuals.

Anti-HIV Agents↗
PubMed2006

Kinetic and molecular evidences that human cardiac muscle express non-M2 muscarinic receptor subtypes that are able to interact themselves.

In heart tissue five isoforms of the muscarinic acetylcholine receptor (mAChR) have been identified, designated m1-m5, of which only M1, M2 and M3 have functional evidences for their role in cardiac physiology. The present study was designed to explore the diversity of mAChR subtypes in human hearts and determine whether these subtypes are able to interact themselves. Expression of mRNAs encoding all five subtypes was readily detected by RT-PCR reaction in both atrial (A) and ventricle (V) samples. Immunoblotting, MABA and ELISA with subtype-specific antibodies confirmed the presence of M1, M2, M3, M4 and M5 proteins in membrane preparations from both A and V. Kinetic characterization using [(3)H]-QNB shown: (1) atrium had greater B(max) than did the ventricle, (2) [(3)H]-QNB behave as an allosteric modulator, inducing cooperativity at high and disclosing heterogeneity at low concentrations, (3) heterogenity was observed in pirenzepine, biperiden and tropicamide competition curves, being the high affinity sites compatible with M1 and M4 muscarinic receptor subtypes and (4) methoctramine competition curves in presence of selective muscarinic receptor subtypes antagonist displayed heterogeneity profile still maintaining cooperativity (n(H)>1), indicating muscarinic receptors subtypes are able to form homo- and hetero-oligomers. In conclusion, our results provide molecular and kinetic evidence for the presence of multiple subtypes of mAChR in human hearts, which are able to undergo discrete transitions from a non-cooperative kinetics of non-interacting monomers to a cooperative kinetics of interacting oligomers.

Adult↗
PubMed2004

The biological effects of five feline IFN-alpha subtypes.

IFN-alpha has been shown to induce both antiviral and antiproliferative activities in animals. This report describes the biological activity of five recently identified feline IFN-alpha subtypes expressed in the Chinese hamster ovary (CHO) cell line (rfeIFN-alpha1[CHO], rfeIFN-alpha2[CHO], rfeIFN-alpha3[CHO], rfeIFN-alpha5[CHO] and rfeIFN-alpha6[CHO]) and the feIFN-alpha6 subtype expressed in and purified from Pichia pastoris (rfeIFN-alpha6[P. pastoris]). The rfeIFN-alpha[CHO] subtypes were tested for antiviral activity against either Vesicular stomatitis virus (VSV) or feline calicivirus (FCV) infected feline embryonic fibroblast cell line (AH927) or Crandell feline kidney cell line (CRFK). Antiviral activity was induced against both VSV and FCV infected AH927 cells and VSV infected CRFK cells by all five of the rfeIFN-alpha[CHO] subtypes and rfeIFN-alpha6[P. pastoris]. In addition, the IFN-alpha inducible Mx gene (associated with antiviral activity) was upregulated in vivo 24 h following treatment with rfeIFN-alpha6[P. pastoris], compared to baseline levels seen prior to treatment. All of the rfeIFN-alpha[CHO] subtypes and rfeIFN-alpha6[P. pastoris] exhibited antiproliferative activity in the FeT-J cell line (an IL-2 independent feline T-cell line). Both necrosis and apoptosis were observed in rfeIFN-alpha6[P. pastoris]-treated FeT-J cells. The rfeIFN-alpha3[CHO] subtype consistently exhibited lower antiviral and antiproliferative activity compared to that observed with the other four rfeIFN-alpha[CHO] subtypes. In summary, this paper demonstrates that five previously described feIFN-alpha subtypes induce both antiviral and antiproliferative activities in vitro and are capable of upregulating the feMx gene in vivo.

Animals↗
PubMed2006

Genetic characteristics of the V3 region associated with CXCR4 usage in HIV-1 subtype C isolates.

CXCR4 coreceptor usage appears to occur less frequently among HIV-1 subtype C viruses. The aim of this study was to investigate the genetic determinants within the V3 region of subtype C isolates able to use CXCR4. Thirty-two subtype C isolates with known phenotypes (16 R5, 8 R5X4 and 8 X4 isolates) were assessed. A subtype C-specific V3 heteroduplex tracking assay (HTA) was used to determine sample complexity, and nucleotide sequencing analysis was used to compare characteristics associated with CCR5 and CXCR4-using isolates. There were sufficient genetic differences to discriminate between R5 viruses and those able to use CXCR4. In general, R5 isolates had an HTA mobility ratio >0.9 whereas CXCR4-using isolates were usually <0.9. Multiple bands were more frequently seen among the dualtropic isolates. Sequence analysis of the V3 region showed that CXCR4-using viruses were often associated with an increased positive amino acid charge, insertions and loss of a glycosylation site, similar to HIV-1 subtype B. In contrast, where subtype B consensus V3 has a GPGR crown motif irrespective of coreceptor usage, all 16 subtype C R5 viruses had a conserved GPGQ sequence at the tip of the loop, while 12 of the 16 (75%) CXCR4-using viruses had substitutions in this motif, most commonly arginine (R). These findings were confirmed using a larger published data set. We therefore suggest that changes within the crown motif of subtype C viruses might be an additional pathway to utilise CXCR4 and thus GPGQ may limit the potential for the development of X4 viruses.

Amino Acid Sequence↗
PubMed2000

Multiple opioid receptors mediate feeding elicited by mu and delta opioid receptor subtype agonists in the nucleus accumbens shell in rats.

The nucleus accumbens, and particularly its shell region, is a critical site at which feeding responses can be elicited following direct administration of opiate drugs as well as micro-selective and delta-selective, but not kappa-selective opioid receptor subtype agonists. In contrast to observations of selective and receptor-specific opioid antagonist effects upon corresponding agonist-induced actions in analgesic studies, ventricular administration of opioid receptor subtype antagonists blocks feeding induced by multiple opioid receptor subtype agonists. The present study examined whether feeding responses elicited by either putative mu ([D-Ala(2), NMe-Phe(4), Gly-ol(5)]-enkephalin (DAMGO)), delta(1) ([D-Pen(2), D-Pen(5)]-enkephalin (DPDPE)) or delta(2) ([D-Ala(2), Glu(4)]-deltorphin (Deltorphin)) opioid receptor subtype agonists administered into the nucleus accumbens shell were altered by accumbens pretreatment with either selective mu (beta-funaltrexamine), mu(1) (naloxonazine), delta(1) ([D-Ala(2), Leu(5), Cys(6)]-enkephalin (DALCE)), delta(2) (naltrindole isothiocyanate) or kappa(1) (nor-binaltorphamine) opioid receptor subtype antagonists. Similar magnitudes and durations of feeding responses were elicited by bilateral accumbens administration of either DAMGO (2.5 microg), DPDPE (5 microg) or Deltorphin (5 microg). DAMGO-induced feeding in the nucleus accumbens shell was significantly reduced by accumbens pretreatment of mu, delta(1), delta(2) and kappa(1), but not mu(1) opioid receptor subtype antagonists. DPDPE-induced feeding in the accumbens was significantly reduced by accumbens pretreatment of mu, delta(1), delta(2) and kappa(1), but not mu(1) opioid receptor subtype antagonists. Deltorphin-induced feeding in the accumbens was largely unaffected by accumbens delta(2) antagonist pretreatment, and was significantly enhanced by accumbens mu or kappa(1) antagonist pretreatment. These data indicate different opioid pharmacological profiles for feeding induced by putative mu, delta(1) and delta(2) opioid agonists in the nucleus accumbens shell, as well as the participation of multiple opioid receptor subtypes in the elicitation and maintenance of feeding by these agonists in the nucleus accumbens shell.

Animals↗