Whole Body Radioautographic Analysis of the In Vivo Distribution of Glucagon Receptors in Mice.

Watanabe, Masaru; Tamayama, Takumi; Hayasaki, Hana; Kuno, Masato; Kuroda, Eriko; Watanabe, Yutaka; Shimada, M.

doi:10.1267/ahc.30.471

Cited by 4 publications

(4 citation statements)

References 35 publications

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“…Indeed, there are plenty of papers indicating the presence of GABA receptors in peripheral tissues including superior cervical ganglion (Farkas et al, 1986), kidney (Amenta et al 1988;Erdö, 1990), adrenal gland (Castro et al, 1989;Martinez et al, 1987), liver (Minuk et al, 1987), urinary bladder (Erdö et al, 1989b), pancreas (Rorsman et al, 1989), stomach (Erdö et al, 1989aNakajima et al, 1996), and intestine (Gentilini et al, 1992;Nakajima et al, 1996). Whole body autoradiographic technique used in the present study was not sensitive enough to distinguish the cells containing GABA receptors, though the technique had proven to be a powerful tool for investigating the tissue distribution of insulin (Watanabe et al, 1992), glucagon (Watanabe et al, 1997b), and epidermal growth factor (Nishihara et al, 1994) receptors. The cellular distribution of GABA receptors should be made by light microscopic autoradiography that provides more sensitivity and resolution (Hirose et al, 1994;Shimada and Watanabe, 1997;Watanabe et al 1997aWatanabe et al , 1998.…”

Section: Discussionmentioning

confidence: 59%

Autoradiographic distribution of radioactivity from 14C-GABA in the mouse

Kuroda

Watanabe

Tamayama

et al. 2000

Microsc. Res. Tech.

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We investigated the distribution of radioactivity from (14)C-labeled gamma-aminobutyric acid (GABA) in the mouse by in vivo autoradiography to clarify the tissues that show GABA uptake and/or GABA binding. Male mice were injected intravenously with (14)C-GABA in both the absence and presence of an excess of unlabeled GABA, baclofen and isoguvacine. Whole-body autoradiography of (3)H-baclofen, a GABA(B) receptor agonist was also performed. At short intervals after (14)C-GABA injection ( 3 and 6 minutes), very high radioactivity was detected in the kidney cortex, liver, pineal gland, hypophysis, median eminence of the hypothalamus, and cervical ganglion. The hyaline cartilage and glandular part of the stomach showed moderate radioactivity. In the presence of an excess amount of unlabeled GABA, radioactivity in most of tissues decreased significantly, but no significant difference in radioactivity was observed in the presence of baclofen and isoguvacine, agonists of GABA(A) and GABA(B) receptors, respectively. Autoradiography of (3)H-baclofen showed that the kidney had high level of radioactivity, whereas the activity in other tissues and organs was similar or lower than in the blood except for the content of the urinary bladder and the pancreas at 15 minutes after injection. These data indicate that radioactivity from incorporated (14)C-GABA into a variety of cells is much higher than that from bound (14)C-GABA to the receptor sites. Our results suggest that GABA can be quickly localized in many organs of the mouse body after 3 minutes following injection, and GABA may serve multiple functions in those organs.

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Section: Discussionmentioning

confidence: 59%

Autoradiographic distribution of radioactivity from 14C-GABA in the mouse

Kuroda

Watanabe

Tamayama

et al. 2000

Microsc. Res. Tech.

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“… Presence of GCGR using IHC staining with antibody no. 11 Presence of GCGR using a radiolabeled ligand Presence of GCGR using RNA-sequencing Studies located GCGR using immunostaining Studies located GCGR using a radiolabeled ligand Liver Yes Yes Yes (scRNA-sequencing indicates specific location primarily within hepatocytes) Previously located in rats, using monoclonal antibody 34 Previously located in mice 51 , 52 Kidney Yes Yes Yes (scRNA-sequencing suggests specific location within collecting and distal tubule cells) Previously located in rats, using monoclonal antibody 34 Located in In vitro 53 – 55 Pancreas Yes Yes Yes (scRNA-sequencing indicates specific location primarily within Beta-cells) Previously located in rats and INS1 cells 25 Previously located in In rats and INS1 cells 25 Duodenum No No No Ileum Yes – No Previously located in mice, small intestine 51 and dog intestinal smooth muscle cells 56 Heart Yes No No Previously located in mice 51 Fat Tissue Yes (Preadipocytes and BAT) No No Previously located in rats, using monoclonal antibody 34 Previously located in mice 51 Adrenal gland Yes (cortical part) No No Gastric mucosa Yes No No …”

Section: Resultsmentioning

confidence: 99%

“…The trend of GCGR expression was visualized in violin plots arranged by the average expression in each cell type in decreasing order. Previously located in rats, using monoclonal antibody 34 Previously located in mice 51,52 Kidney Yes Yes Yes (scRNAsequencing suggests specific location within collecting and distal tubule cells)…”

Section: Methodsmentioning

confidence: 99%

Evaluation of commercially available glucagon receptor antibodies and glucagon receptor expression

et al. 2022

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Glucagon is a major regulator of metabolism and drugs targeting the glucagon receptor (GCGR) are being developed. Insight into tissue and cell-specific expression of the GCGR is important to understand the biology of glucagon and to differentiate between direct and indirect actions of glucagon. However, it has been challenging to localize the GCGR in tissue due to low expression levels and lack of specific methods. Immunohistochemistry has frequently been used for GCGR localization, but antibodies targeting G-protein-coupled-receptors may be inaccurate. We evaluated all currently commercially available GCGR antibodies. The antibody, ab75240 (Antibody no. 11) was found to perform best among the twelve antibodies tested and using this antibody we found expression of the GCGR in the kidney, liver, preadipocytes, pancreas, and heart. Three antibody-independent approaches all confirmed the presence of the GCGR within the pancreas, liver and the kidneys. GCGR expression should be evaluated by both antibody and antibody-independent approaches.

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“…Taking a pharmacokinetic approach, non-peptide antagonists at the glucagon receptor have been developed that are per-orally available and might play a role in treating diabetes [ 12 , 119 ]. Some authors have claimed that glucagon fails to pass through the blood–brain barrier [ 121 ]. Hence, glucagon infused to treat the heart should not have direct side effects in the brain.…”

Section: Glucagon Receptor Agonists and Antagonistsmentioning

confidence: 99%

Glucagon and Its Receptors in the Mammalian Heart

Neumann

Hofmann

Dhein

et al. 2023

IJMS

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Glucagon exerts effects on the mammalian heart. These effects include alterations in the force of contraction, beating rate, and changes in the cardiac conduction system axis. The cardiac effects of glucagon vary according to species, region, age, and concomitant disease. Depending on the species and region studied, the contractile effects of glucagon can be robust, modest, or even absent. Glucagon is detected in the mammalian heart and might act with an autocrine or paracrine effect on the cardiac glucagon receptors. The glucagon levels in the blood and glucagon receptor levels in the heart can change with disease or simultaneous drug application. Glucagon might signal via the glucagon receptors but, albeit less potently, glucagon might also signal via glucagon-like-peptide-1-receptors (GLP1-receptors). Glucagon receptors signal in a species- and region-dependent fashion. Small molecules or antibodies act as antagonists to glucagon receptors, which may become an additional treatment option for diabetes mellitus. Hence, a novel review of the role of glucagon and the glucagon receptors in the mammalian heart, with an eye on the mouse and human heart, appears relevant. Mouse hearts are addressed here because they can be easily genetically modified to generate mice that may serve as models for better studying the human glucagon receptor.

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Whole Body Radioautographic Analysis of the In Vivo Distribution of Glucagon Receptors in Mice.

Cited by 4 publications

References 35 publications

Autoradiographic distribution of radioactivity from 14C-GABA in the mouse

Autoradiographic distribution of radioactivity from 14C-GABA in the mouse

Evaluation of commercially available glucagon receptor antibodies and glucagon receptor expression

Glucagon and Its Receptors in the Mammalian Heart

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