Autoradiographic investigation of the distribution of [14C]GABA in tissues of normal and aminooxyacetic acid-treated mice

Hespe, W.; Roberts, Eugene; Prins, Hans W.

doi:10.1016/0006-8993(69)90206-6

Cited by 33 publications

(8 citation statements)

References 14 publications

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“…Most of the GABA Uptake by Hepatocytes Is Catalyzed by GAT2-This study agrees with previous reports that uptake of GABA in the liver is predominantly due to GAT2 (12)(13)(14). First, the substrate selectivity matches that of GAT2.…”

Section: Gat2 Is the Major Taurine Transporter In Hepatocytes Atsupporting

confidence: 91%

“…In fact, the GABA concentration in portal venous blood is significantly higher than that in arterial blood (79), and whole body autoradiography following injection of radioactively labeled GABA shows that most of the GABA is taken up by the liver (12,13). Together, this suggests that the liver is the primary organ responsible for GABA clearance from systemic circulation and that GAT2 is the transporter involved.…”

Section: Gat2 Is the Major Taurine Transporter In Hepatocytes Atmentioning

confidence: 99%

“…Outside the central nervous system, GABA uptake has been described in liver and kidney in vivo (12,13) and in vitro (14,15), and GABA may play a signaling role in peripheral organs, including the immune system (16,17). GAT2 is a promising candidate for peripheral GABA uptake (2, 4, 6, 18 -23).…”

mentioning

confidence: 99%

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Deletion of the γ-Aminobutyric Acid Transporter 2 (GAT2 and SLC6A13) Gene in Mice Leads to Changes in Liver and Brain Taurine Contents

Zhou

Holmseth

Guo

et al. 2012

Journal of Biological Chemistry

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Background:The physiological roles of GABA transporter 2 (GAT2) are unknown. Results: Deletion of the GAT2 gene reduced liver taurine levels but increased brain levels. Conclusion: GAT2 is unimportant for inactivation of neurotransmitter GABA. Instead, GAT2 is a major taurine transporter in hepatocytes and an efflux transporter at the blood-brain barrier. Significance: GAT2 knockout mice will be crucial for uncovering the roles of GAT2.

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Section: Gat2 Is the Major Taurine Transporter In Hepatocytes Atsupporting

confidence: 91%

Section: Gat2 Is the Major Taurine Transporter In Hepatocytes Atmentioning

confidence: 99%

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Deletion of the γ-Aminobutyric Acid Transporter 2 (GAT2 and SLC6A13) Gene in Mice Leads to Changes in Liver and Brain Taurine Contents

Zhou

Holmseth

Guo

et al. 2012

Journal of Biological Chemistry

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“…In fact, changes in the blood-brain barrier permeability have been suggested as a possible explanation for the discrepancy between the serum GABA level and the clinical stage of HE. GABA ordinarily does not pass the blood-brain barrier (21,22) although, in animal models of acute liver failure, an altered blood-brain barrier has been suggested in order to explain increased GABA entry into the brain (23). Conversely, in other experimental studies, neither H-GABA brain content after i.v.…”

Section: Discussionmentioning

confidence: 99%

Hepatic encephalopathy: Lack of changes of γ-aminobutyric acid content in plasma and cerebrospinal fluid

Moroni¹,

Riggio²,

Carlà³

et al. 1987

Hepatology

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The aim of the study was to verify the role of gamma-aminobutyric acid in the pathogenesis of hepatic encephalopathy occurring in cirrhotic patients by attempting to correlate plasma and cerebrospinal fluid content of authentic gamma-aminobutyric acid with the neurological manifestations of hepatic encephalopathy. For this purpose, plasma and cerebrospinal fluid gamma-aminobutyric acid levels were measured by means of mass fragmentography in 17 cirrhotic patients with hepatic encephalopathy and in 6 cirrhotics without neurological symptoms. Moreover, in all patients, a second sample was obtained during the clinical course of hepatic encephalopathy. The mean plasma and cerebrospinal fluid gamma-aminobutyric acid levels were not different in patients with or without hepatic encephalopathy and did not change during the evolution of the neurological symptoms. The lack of changes in the gamma-aminobutyric acid content in plasma and cerebrospinal fluid during hepatic encephalopathy is in contrast with the hypothesized importance of increased entry into the brain of gamma-aminobutyric acid in the pathogenesis of hepatic encephalopathy.

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“…Autoradiography also showed that excretion of injected GABA occurred very rapidly through the urinary system. Although the distribution of 14 C-GABA in tissues of female mice had already been investigated by whole body autoradiography (Hespe et al, 1969), nothing is known about the distribution of radioactivity at intervals earlier than one hour after injection. The distribution pattern 1 hour after radioactive GABA injection reported by Hespe et al (1969) was in agreement with that of the present study.…”

Section: Discussionmentioning

confidence: 99%

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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Autoradiographic investigation of the distribution of [14C]GABA in tissues of normal and aminooxyacetic acid-treated mice

Cited by 33 publications

References 14 publications

Deletion of the γ-Aminobutyric Acid Transporter 2 (GAT2 and SLC6A13) Gene in Mice Leads to Changes in Liver and Brain Taurine Contents

Deletion of the γ-Aminobutyric Acid Transporter 2 (GAT2 and SLC6A13) Gene in Mice Leads to Changes in Liver and Brain Taurine Contents

Hepatic encephalopathy: Lack of changes of γ-aminobutyric acid content in plasma and cerebrospinal fluid

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

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