Digital Commons Network^™

Fluorinated N,N'-Diarylureas As Novel Therapeutic Agents Against Cancer Stem Cells, Dasha E. Kenlan, Piotr G. Rychahou, Vitaliy M. Sviripa, Heidi L. Weiss, Chunming Liu, David S. Watt, B. Mark Evers

Markey Cancer Center Faculty Publications

Colorectal cancer is the second-leading cause of cancer-related mortality in the United States. More than 50% of patients with colorectal cancer will develop local recurrence or distant organ metastasis. Cancer stem cells play a major role in the survival and metastasis of cancer cells. In this study, we examined the effects of novel AMP-activated protein kinase (AMPK) activating compounds on colorectal cancer metastatic and stem cell lines as potential candidates for chemotherapy. We found that activation of AMPK by all fluorinated N,N-diarylureas (FND) compounds at micromolar levels significantly inhibited the cell-cycle progression and subsequent cellular proliferation. In addition, we demonstrated …

Paracrine Regulation Of Melanocyte Genomic Stability: A Focus On Nucleotide Excision Repair, Stuart Gordon Jarrett, Katharine Marie Carter, John August D'Orazio

Markey Cancer Center Faculty Publications

UV radiation is a major environmental risk factor for the development of melanoma by causing DNA damage and mutations. Resistance to UV damage is largely determined by the capacity of melanocytes to respond to UV injury by repairing mutagenic photolesions. The nucleotide excision repair (NER) pathway is the major mechanism by which cells correct UV photodamage. This multistep process involves the basic steps of damage recognition, isolation, localized strand unwinding, assembly of a repair complex, excision of the damage‐containing strand 3′ and 5′ to the photolesion, synthesis of a sequence‐appropriate replacement strand, and finally ligation to restore continuity of genomic …

Metformin To Augment Strength Training Effective Response In Seniors (Masters): Study Protocol For A Randomized Controlled Trial, Doug E. Long, Bailey D. Peck, Jenny L. Martz, S. Craig Tuggle, Heather M. Bush, Gerald Mcgwin, Philip A. Kern, Marcas M. Bamman, Charlotte A. Peterson

Clinical and Translational Science Faculty Publications

Background: Muscle mass and strength are strong determinants of a person's quality of life and functional independence with advancing age. While resistance training is the most effective intervention to combat age-associated muscle atrophy (sarcopenia), the ability of older adults to increase muscle mass and strength in response to training is blunted and highly variable. Thus, finding novel ways to complement resistance training to improve muscle response and ultimately quality of life among older individuals is critical. The purpose of this study is to determine whether a commonly prescribed medication called metformin can be repurposed to improve the response to resistance …

Genome-Wide Analysis Of Atp-Binding Cassette (Abc) Transporters In The Sweetpotato Whitefly, Bemisia Tabaci, Lixia Tian, Tianxue Song, Rongjun He, Yang Zeng, Wen Xie, Qingjun Wu, Shaoli Wang, Xuguo Zhou, Youjun Zhang

Entomology Faculty Publications

Background: ABC transporter superfamily is one of the largest and ubiquitous groups of proteins. Because of their role in detoxification, insect ABC transporters have gained more attention in recent years. In this study, we annotated ABC transporters from a newly sequenced sweetpotato whitefly genome. Bemisia tabaci Q biotype is an emerging global invasive species that has caused extensive damages to field crops as well as ornamental plants.

Results: A total of 55 ABC transporters containing all eight described subfamilies (A to H) were identified in the B. tabaci Q genome, including 8 ABCAs, 3 ABCBs, 6 ABCCs, 2 ABCDs, 1 …

Functional Human Grin2b Promoter Polymorphism And Variation Of Mental Processing Speed In Older Adults, Yang Jiang, Ming Kuan Lin, Gregory A. Jicha, Xiuhua Ding, Sabrina L. Mcilwrath, David W. Fardo, Lucas S. Broster, Frederick A. Schmitt, Richard J. Kryscio, Robert H. Lipsky

Behavioral Science Faculty Publications

We investigated the role of a single nucleotide polymorphism rs3764030 (G > A) within the human GRIN2B promoter in mental processing speed in healthy, cognitively intact, older adults. In vitro DNA-binding and reporter gene assays of different allele combinations in transfected cells showed that the A allele was a gain-of-function variant associated with increasing GRIN2B mRNA levels. We tested the hypothesis that individuals with A allele will have better memory performance (i.e. faster reaction times) in older age. Twenty-eight older adults (ages 65-86) from a well-characterized longitudinal cohort were recruited and performed a modified delayed match-to-sample task. The rs3764030 polymorphism was …

Chronic Neuropsychological Sequelae In A Patient With Nontumorous Anti-Nmda-Receptor Encephalitis, Dong Y. Han, Lisa M. Mason, Aarti Patel, Zhengqiu Zhou, Sarah Phillips, Siddharth Kapoor

Neurology Faculty Publications

Anti-N-methyl-D-aspartate receptor encephalitis is a neurological, autoimmune disorder tightly conceptualized only as recently as the mid-2000s. It presents itself in a combination of psychiatric, neurological, and autonomic features. We observe a unique case with probable earlier episode (prior to the mid-2000s conceptualization of the disease) and a later relapse, accompanying a comprehensive neuropsychological profile tracked after the relapse and subsequent improvement. Neurocognitive findings revealed residual frontal deficits with mood changes even in the state after plasmapheresis. This case is the first to describe posttreatment cognition in anti-NMDAR encephalitis after probable serial autoimmune episodes.

Gregariousness Does Not Vary With Geography, Developmental Stage, Or Group Relatedness In Feeding Redheaded Pine Sawfly Larvae, John W. Terbot Ii, Ryan L. Gaynor, Catherine R. Linnen

Biology Faculty Publications

Aggregations are widespread across the animal kingdom, yet the underlying proximate and ultimate causes are still largely unknown. An ideal system to investigate this simple, social behavior is the pine sawfly genus Neodiprion, which is experimentally tractable and exhibits interspecific variation in larval gregariousness. To assess intraspecific variation in this trait, we characterized aggregative tendency within a single widespread species, the redheaded pine sawfly (N. lecontei). To do so, we developed a quantitative assay in which we measured interindividual distances over a 90-min video. This assay revealed minimal behavioral differences: (1) between early-feeding and late-feeding larval instars, …

Evaluation Of Six Serological Elisa Kits Available In Italy As Screening Tests For Equine Infectious Anaemia Surveillance, Roberto Nardini, Gian Luca Autorino, Charles J. Issel, Richard F. Cook, Ida Ricci, Raffaele Frontoso, Francesca Rosone, Maria Teresa Scicluna

Maxwell H. Gluck Equine Research Center Faculty Publications

Background: ELISAs are known to have a higher diagnostic sensitivity than the agar gel immunodiffusion (AGID) when employed for serological diagnosis of equine infectious anaemia (EIA). For this purpose, an “in-house” and five commercial ELISAs available in Italy were assessed by the National Reference Centre for EIA for their analytic specificity (Sp); precocity, defined as capability of detecting first antibodies produced during a new infection; precision based on repeatability and reproducibility, estimated from the coefficient of variation (CV); accuracy, estimated from multiple K and relative Sp and sensitivity (Se). Two serum panels, positive for non-equine retroviruses and the most frequent …

Glucans And The Poultry Immune System, Jacquie Jacob, Anthony J. Pescatore

Animal and Food Sciences Faculty Publications

With the reduced availability of antibiotics, poultry producers are looking for feed additives to stimulate the immune system of their birds. Some beta-glucans have been shown to improve gut health in poultry subjected to a bacterial challenge, to increase the flow of new immunocytes into the various lymphoid organs, to increase macrophage function, to increase antibody titers after a vaccination and to function as an anti-inflammatory immunomodulator. As a result, beta-glucans may provide a tool for producers trying to reduce or eliminate the use of antibiotics in poultry diets.

Granulosa Cell Endothelin-2 Expression Is Fundamental For Ovulatory Follicle Rupture, Joseph A. Cacioppo, Po-Ching Patrick Lin, Patrick R. Hannon, Daniel R. Mcdougle, Arnon Gal, Chemyong Ko

Obstetrics and Gynecology Faculty Publications

Ovulation is dependent upon numerous factors mediating follicular growth, vascularization, and ultimately oocyte release via follicle rupture. Endothelin-2 (EDN2) is a potent vasoconstrictor that is transiently produced prior to follicle rupture by granulosa cells of periovulatory follicles and induces ovarian contraction. To determine the role of Edn2 expression, surgical transplant and novel conditional knockout mice were super-ovulated and analyzed. Conditional knockout mice utilized a new iCre driven by the Esr2 promoter to selectively remove Edn2. Follicle rupture and fertility were significantly impaired in the absence of ovarian Edn2 expression. When ovaries of Edn2KO mice were transplanted in wild type …

Pharmacology, Pharmacokinetics, And Metabolism Of The Dna-Decoy Ayx1 For The Prevention Of Acute And Chronic Post-Surgical Pain, Julien Mamet, Scott Harris, Michael Klukinov, David C. Yeomans, Renee R. Donahue, Bradley K. Taylor, Kelly Eddinger, Tony Yaksh, Donald C. Manning

Physiology Faculty Publications

Background: AYX1 is an unmodified DNA-decoy designed to reduce acute post-surgical pain and its chronification with a single intrathecal dose at the time of surgery. AYX1 inhibits the transcription factor early growth response protein 1, which is transiently induced at the time of injury and triggers gene regulation in the dorsal root ganglia and spinal cord that leads to long-term sensitization and pain. This work characterizes the AYX1 dose-response profile in rats and the link to AYX1 pharmacokinetics and metabolism in the cerebrospinal fluid, dorsal root ganglia, and spinal cord.

Results: The effects of ascending dose-levels of AYX1 on mechanical …

Evaluation Of Circulating Mirnas During Late Pregnancy In The Mare, Shavahn C. Loux, Kirsten E. Scoggin, Jason E. Bruemmer, Igor F. Canisso, Mats H. T. Troedsson, Edward L. Squires, Barry A. Ball

Veterinary Science Faculty Publications

MicroRNAs (miRNAs) are small, non-coding RNAs which are produced throughout the body. Individual tissues tend to have a specific expression profile and excrete many of these miRNAs into circulation. These circulating miRNAs may be diagnostically valuable biomarkers for assessing the presence of disease while minimizing invasive testing. In women, numerous circulating miRNAs have been identified which change significantly during pregnancy-related complications (e.g. chorioamnionitis, eclampsia, recurrent pregnancy loss); however, no prior work has been done in this area in the horse. To identify pregnancy-specific miRNAs, we collected serial whole blood samples in pregnant mares at 8, 9, 10 m of gestation …

Out In The Cold: Ingredients In Over-The-Counter Cold Medicines Can Wreak Havod On A Trainer's Livelihood And An Owner's Prized Racehorse, Clara Fenger, Tanya Boulmetis, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

No abstract provided.

Retention Of Normal Glia Function By An Isoform-Selective Protein Kinase Inhibitor Drug Candidate That Modulates Cytokine Production And Cognitive Outcomes, Zhengqiu Zhou, Adam D. Bachstetter, Claudia B. Späni, Saktimayee M. Roy, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Background: Brain p38α mitogen-activated protein kinase (MAPK), a potential therapeutic target for cognitive dysfunction based on the neuroinflammation-synaptic dysfunction cycle of pathophysiology progression, offers an innovative pharmacological strategy via inhibiting the same activated target in both glia and neurons, thereby enhancing the possibility for efficacy. The highly selective, brain-penetrant p38αMAPK inhibitor MW150 attenuates cognitive dysfunction in two distinct Alzheimer's disease (AD)-relevant models and avoids the problems encountered with previous mixed-kinase inhibitor drug candidates. Therefore, it is essential that the glial effects of this CNS-active kinase inhibitor be addressed in order to anticipate future use in clinical investigations.

Methods: …

Forage News [2017-04], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• Dealing with Frost Damaged Alfalfa
• Managing Spring Grass Growth
• Utilizing Frosted Small Grains for Forage

A Compromised Liver Alters Polychlorinated Biphenyl-Mediated Toxicity, Banrida Wahlang, Jordan T. Perkins, Michael C. Petriello, Jessie B. Hoffman, Arnold J. Stromberg, Bernhard Hennig

Superfund Research Center Faculty Publications

Exposure to environmental toxicants namely polychlorinated biphenyls (PCBs) is correlated with multiple health disorders including liver and cardiovascular diseases. The liver is important for both xenobiotic and endobiotic metabolism. However, the responses of an injured liver to subsequent environmental insults has not been investigated. The current study aims to evaluate the role of a compromised liver in PCB-induced toxicity and define the implications on overall body homeostasis. Male C57Bl/6 mice were fed either an amino acid control diet (CD) or a methionine-choline deficient diet (MCD) during the 12-week study. Mice were subsequently exposed to either PCB126 (4.9 mg/kg) or the …

Clinical Applications Of Near-Infrared Diffuse Correlation Spectroscopy And Tomography For Tissue Blood Flow Monitoring And Imaging, Yu Shang, Ting Li, Guoqiang Yu

Biomedical Engineering Faculty Publications

Objective. Blood flow is one such available observable promoting a wealth of physiological insight both individually and in combination with other metrics.

Approach. Near-infrared diffuse correlation spectroscopy (DCS) and, to a lesser extent, diffuse correlation tomography (DCT), have increasingly received interest over the past decade as noninvasive methods for tissue blood flow measurements and imaging. DCS/DCT offers several attractive features for tissue blood flow measurements/imaging such as noninvasiveness, portability, high temporal resolution, and relatively large penetration depth (up to several centimeters).

Main results. This review first introduces the basic principle and instrumentation of DCS/DCT, followed by presenting …

Fibroblast Reticular Cells Engineer A Blastema Extracellular Network During Digit Tip Regeneration In Mice, Luis Marrero, Jennifer Simkin, Mimi Sammarco, Ken Muneoka

Biology Faculty Publications

The regeneration blastema which forms following amputation of the mouse digit tip is composed of undifferentiated cells bound together by an organized network of fibers. A monoclonal antibody (ER‐TR7) that identifies extracellular matrix (ECM) fibers produced by fibroblast reticular cells during lymphoid organogenesis was used to characterize the ECM of the digit, the blastema, and the regenerate. Digit fibroblast reticular cells produce an ER‐TR7⁺ ECM network associated with different tissues and represent a subset of loose connective tissue fibroblasts. During blastema formation there is an upregulation of matrix production that returns to its pre‐existing level and anatomical pattern in …

Nephrotoxicity In Patients With Or Without Cystic Fibrosis Treated With Polymyxin B Compared To Colistin, Ryan L. Crass, Wilbur Cliff Rutter, Donna R. Burgess, Craig A. Martin, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Nephrotoxicity is the primary adverse effect of the polymyxins. The relative rates of toxicity of polymyxin B and colistin have not been fully elucidated, especially in patients with cystic fibrosis (CF). A retrospective cohort study of adults treated with polymyxin B or colistin for at least 48 h was conducted. The primary endpoint was the incidence of kidney injury assessed by RIFLE (i.e., risk, injury, failure, loss, end-stage renal disease) criteria. Risk factors for kidney injury were evaluated using multivariate Cox regression. A total of 414 patients were evaluated, 220 of whom had CF. In patients without CF, there was …

Disappearance And Appearance Of An Indigestible Marker In Feces From Growing Pigs As Affected By Previous- And Current-Diet Composition, Brandy M. Jacobs, John F. Patience, Merlin D. Lindemann, Kenneth J. Stalder, Brian J. Kerr

Animal and Food Sciences Faculty Publications

Background: Indigestible markers are commonly utilized in digestion studies, but the complete disappearance or maximum appearance of a marker in feces can be affected by diet composition, feed intake, or an animal’s BW. The objectives of this study were to determine the impact of previous (Phase 1, P1) and current- (Phase 2, P2) diet composition on marker disappearance (Cr) and appearance (Ti) in pigs fed 3 diets differing in NDF content.

Results: When pigs were maintained on the 25.1, 72.5, and 125.0 g/kg NDF diets, it took 5.1, 4.1, and 2.5 d, respectively, for Cr levels to decrease below the …

Overcoming Hurdles To Development Of A Vaccine Against Pneumocystis Jirovecii, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Development of Pneumocystis pneumonia (PCP) is a common problem among immunosuppressed individuals. There are windows of opportunity in which vaccination would be beneficial, but to date, no vaccines have made it to clinical trials. Significant hurdles to vaccine development include host range specificity, making it difficult to translate from animal models to humans. Discovery of cross-reactive epitopes is critical to moving vaccine candidates from preclinical animal studies to clinical trials.

Rod-Shaped Microglia Morphology Is Associated With Aging In 2 Human Autopsy Series, Adam D. Bachstetter, Eseosa T. Ighodaro, Yasmin Hassoun, Danah Aldeiri, Janna H. Neltner, Ela Patel, Erin L. Abner, Peter T. Nelson

Spinal Cord and Brain Injury Research Center Faculty Publications

A subtype of microglia is defined by the morphological appearance of the cells as rod-shaped. Little is known about this intriguing cell type, as there are only a few case reports describing rod-shaped microglia in the neuropathological literature. Rod-shaped microglia were shown recently to account for a substantial proportion of the microglia cells in the hippocampus of both demented and cognitively intact aged individuals. We hypothesized that aging could be a defining feature in the occurrence of rod-shaped microglia. To test this hypothesis, two independent series of autopsy cases (total n=168 cases), which covered the adult lifespan from 20 – …

Thiamine Deficiency Induces Endoplasmic Reticulum Stress And Oxidative Stress In Human Neurons Derived From Induced Pluripotent Stem Cells, Xin Wang, Mei Xu, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem …

Carisbamate Blockade Of T-Type Voltage-Gated Calcium Channels, Do Young Kim, Fang-Xiong Zhang, Stan T. Nakanishi, Timothy Mettler, Ik-Hyun Cho, Younghee Ahn, Florian Hiess, Lina Chen, Patrick G. Sullivan, S. R. Wayne Chen, Gerald W. Zamponi, Jong M. Rho

Spinal Cord and Brain Injury Research Center Faculty Publications

Objectives

Carisbamate (CRS) is a novel monocarbamate compound that possesses antiseizure and neuroprotective properties. However, the mechanisms underlying these actions remain unclear. Here, we tested both direct and indirect effects of CRS on several cellular systems that regulate intracellular calcium concentration [Ca²⁺]_i.

Methods

We used a combination of cellular electrophysiologic techniques, as well as cell viability, Store Overload‐Induced Calcium Release (SOICR), and mitochondrial functional assays to determine whether CRS might affect [Ca²⁺]_i levels through actions on the endoplasmic reticulum (ER), mitochondria, and/or T‐type voltage‐gated Ca²⁺ channels.

Results

In CA3 pyramidal neurons, kainic …

Tumor Necrosis Factor Alpha-Induced Recruitment Of Inflammatory Mononuclear Cells Leads To Inflammation And Altered Brain Development In Murine Cytomegalovirus-Infected Newborn Mice, Maria C. Seleme, Kate Kosmac, Stipan Jonjic, William J. Britt

Physical Therapy Faculty Publications

Congenital human cytomegalovirus (HCMV) infection is a significant cause of abnormal neurodevelopment and long-term neurological sequelae in infants and children. Resident cell populations of the developing brain have been suggested to be more susceptible to virus-induced cytopathology, a pathway thought to contribute to the clinical outcomes following intrauterine HCMV infection. However, recent findings in a newborn mouse model of the infection in the developing brain have indicated that elevated levels of proinflammatory mediators leading to mononuclear cell activation and recruitment could underlie the abnormal neurodevelopment. In this study, we demonstrate that treatment with tumor necrosis factor alpha (TNF-α)-neutralizing …

Acute Effects Of Implantable Cardioverter-Defibrillator Shocks On Biomarkers Of Myocardial Injury, Apoptosis, Heart Failure, And Systemic Inflammation, Jordan Brewster, Travis Sexton, Gary Dhaliwal, Richard Charnigo, Gustavo Morales, Kevin Parrott, Yousef Darrat, John C. Gurley, Susan S. Smyth, Claude S. Elayi

Internal Medicine Faculty Publications

Background: Implantable cardioverter‐defibrillator (ICD) shocks are potentially associated with myocardial injury, altered hemodynamics, apoptosis, and inflammatory signaling. Their precise cellular impact can be explored after defibrillation testing (DFT) via biomarkers. We evaluated changes in biomarkers after ICD shocks during DFT.

Methods: We prospectively enrolled outpatients presenting for first implantation of a cardiac device. Biomarkers indicative of myocardial injury, inflammation, and apoptosis were measured before and after implantation, and compared between patients receiving DFT (DFT+) to those not (DFT−).

Results: Sixty‐three patients were enrolled, 40 in the DFT+ group and 23 in the DFT− group. Average levels of troponin I, hsCRP, …

Social Buffering In A Eusocial Invertebrate: Termite Soldiers Reduce The Lethal Impact Of Competitor Cues On Workers, Li Tian, Evan L. Preisser, Kenneth F. Haynes, Xuguo Zhou

Entomology Faculty Publications

While the impact of predator‐induced stress on prey has received considerable attention, there has been far less research into the effect of competitors. Cues from aggressive competitors should be particularly likely to evoke behavioral and/or physiological responses, since they may be indicative of both direct (interference) and indirect (exploitative) threats. The danger posed by such competitors, and the “fear” they evoke, should be reduced at lower competitor densities and by the presence of individual conspecifics specialized for defense. We assessed how Reticulitermes flavipes termite workers and soldiers were affected by cues from conspecific nestmates, conspecific non‐nestmates, and the heterospecific competitor …

Transcriptional Signatures Of Brain Aging And Alzheimer's Disease: What Are Our Rodent Models Telling Us?, Kendra E. Hargis, Eric M. Blalock

Pharmacology and Nutritional Sciences Faculty Publications

Aging is the biggest risk factor for idiopathic Alzheimer’s disease (AD). Recently, the National Institutes of Health released AD research recommendations that include: appreciating normal brain aging, expanding data-driven research, using open-access resources, and evaluating experimental reproducibility. Transcriptome data sets for aging and AD in humans and animal models are available in NIH-curated, publically accessible databases. However, little work has been done to test for concordance among those molecular signatures. Here, we test the hypothesis that brain transcriptional profiles from animal models recapitulate those observed in the human condition. Raw transcriptional profile data from twenty-nine studies were analyzed to produce …

Exogenous Lactobacilli Mitigate Microbial Changes Associated With Grain Fermentation (Corn, Oats, And Wheat) By Equine Fecal Microflora Ex Vivo, Brittany E. Harlow, Laurie M. Lawrence, Patricia A. Harris, Glen E. Aiken, Michael D. Flythe

Animal and Food Sciences Faculty Publications

Cereal grains are often included in equine diets. When starch intake exceeds foregut digestion starch will reach the hindgut, impacting microbial ecology. Probiotics (e.g., lactobacilli) are reported to mitigate GI dysbioses in other species. This study was conducted to determine the effect of exogenous lactobacilli on pH and the growth of amylolytic and lactate-utilizing bacteria. Feces were collected from 3 mature geldings fed grass hay with access to pasture. Fecal microbes were harvested by differential centrifugation, washed, and re-suspended in anaerobic media containing ground corn, wheat, or oats at 1.6% (w/v) starch and one of five …

GabaB Receptor Attenuation Of GabaA Currents In Neurons Of The Mammalian Central Nervous System, Wen Shen, Changlong Nan, Peter T. Nelson, Harris Ripps, Malcolm M. Slaughter

Pathology and Laboratory Medicine Faculty Publications

Ionotropic receptors are tightly regulated by second messenger systems and are often present along with their metabotropic counterparts on a neuron's plasma membrane. This leads to the hypothesis that the two receptor subtypes can interact, and indeed this has been observed in excitatory glutamate and inhibitory GABA receptors. In both systems the metabotropic pathway augments the ionotropic receptor response. However, we have found that the metabotropic GABA_B receptor can suppress the ionotropic GABA_A receptor current, in both the in vitro mouse retina and in human amygdala membrane fractions. Expression of amygdala membrane microdomains in Xenopus oocytes by microtransplantation …