A γ-aminobutyrate pathway in mammalian kidney cortex☆

Lancaster, Gerald; Mohyuddin, Fazl; Scriver, Charles R.; Whelan, Donald T.

doi:10.1016/0304-4165(73)90069-x

Cited by 51 publications

(30 citation statements)

References 10 publications

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“…The pertinent clinical information and diagnoses are listed in Table 1. If the G A D assay was not performed immediately, the intact tissue was stored at -20°; G A D and GABA are stable under these conditions (8). The outer renal cortex was shaved from the frozen block of tissue and only this portion of kidney was used for assay to avoid dilution of activity with medulla, which contains little G A D or GABA (22).…”

Section: Methods a N D Materials Source O F Tissuementioning

confidence: 99%

“…In this fashion, the formation of a titratable organic acid derived from glutamate can be avoided during repair of acid-base imbalance. We have shown that about one-third of endogenous glutamate oxidation in renal cortex of the rat takes place via the GABA pathway (8).…”

mentioning

confidence: 89%

“…T h e tissue was tissue. homogenized and deproteinized before analysis as described fn the absence of PLP-saturation of G A D apoenzyme in vitro, previously (8).…”

Section: Gaba Determinationmentioning

confidence: 99%

“…In previous publications (8,19,22) we described the presence of a pathway in mammalian kidney which forms GABA by the decarboxylation of L-glutamate and which then delivers the GABA via succinic semialdehyde to the tricarboxylic acid cycle. W e postulated (8) :hat the pathway can be an effective means of disposal for the carbon chain of glutamate when it is produced from L-glutamine during renal ammoniagenesis.…”

mentioning

confidence: 99%

“…W e postulated (8) :hat the pathway can be an effective means of disposal for the carbon chain of glutamate when it is produced from L-glutamine during renal ammoniagenesis. Conversion of glutamate, first to GABA, and then to succinate, bypasses the formation of a-ketoglutarate which is necessary if glutamate is converted to succinate via the Krebs cycle.…”

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confidence: 99%

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Ontogeny of L-Glutamic Acid Decarboxylase and γ-Aminobutyric Acid Concentration in Human Kidney

1975

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Pediat. Res. 9: 484-487 (1975) Extract particular importance in man, who extracts glutamine from the Mature human renal cortex contains y-aminobutyric acid (GABA) at concentrations on the order of 0.2 p n o l / g wet wt and about half of that concentration in fetal kidney.a -A m i n o b u t y r i c acid h u m a n kidney g l u t a m i c acid decarboxylase pyridoxal p h o s p h a tThe pyridoxal-5'-phosphate (PLP)-dependent enzyme, Lglutamic acid decarboxylase (GAD), catalyzes the conversion of L-glutamate to GABA. The PLP-saturated GAD activity in post-term ( 1 day-9 years) renal cortex homogenate is 0.94 A 0.38 p n o l CO, formed/g wet wt/hr (Table 1). The corresponding GAD activity in fetal renal cortex, in the midtrimester and early third trimester, is 0.28 0.19 p n o l CO, formed/g wet wt/hr (P < 0.01 vs. post-term activity). GAD activity increases during gestation to reach levels at birth equivalent to mature kidney. When corrections are made for the difference in tissue water between fetal and mature kidney, they do not ablate the post-term increase in GAD activity.Renal GAD was undersaturated with P L P in 12 of 21 specimens examined; 8 of these specimens were of fetal origin (Table 1 and Fig. 2). Undersaturation was revealed when addition of P L P (0.24 m M ) to the homogenate stimulated activity by 2 5 3 0 0 % in the 12 specimens. GAD activity in rat kidney binds P L P avidly and is always saturated with P L P under the normal laboratory conditions of vitamin B, nutrition. Undersaturation of renal GAD in man may imply inadequate endogenous availability of vitamin B, coenzyme.The GABA pathway in mammalian kidney has been implicated in the maintenance of normal acid-base balance. Renal G A D is increased in the postnatal subject relative to fetal GAD activity in support of this hypothesis. Undersaturation of fetal GAD with its PLP-coenzyme in two-thirds of the fetal specimens may have implications concerning intrauterine nutrition and renal development.

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Section: Methods a N D Materials Source O F Tissuementioning

confidence: 99%

mentioning

confidence: 89%

“…T h e tissue was tissue. homogenized and deproteinized before analysis as described fn the absence of PLP-saturation of G A D apoenzyme in vitro, previously (8).…”

Section: Gaba Determinationmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Ontogeny of L-Glutamic Acid Decarboxylase and γ-Aminobutyric Acid Concentration in Human Kidney

1975

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Autoradiographic distribution of radioactivity from14C-GABA in the mouse

Kuroda

Watanabe

Tamayama

et al. 2000

Microsc. Res. Tech.

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We investigated the distribution of radioactivity from 14C‐labeled γ‐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 14C‐GABA in both the absence and presence of an excess of unlabeled GABA, baclofen and isoguvacine. Whole‐body autoradiography of 3H‐baclofen, a GABAB receptor agonist was also performed. At short intervals after 14C‐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 GABAA and GABAB receptors, respectively. Autoradiography of 3H‐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 14C‐GABA into a variety of cells is much higher than that from bound 14C‐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. Microsc. Res. Tech. 41:116–126, 2000. © 2000 Wiley‐Liss, Inc.

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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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A γ-aminobutyrate pathway in mammalian kidney cortex☆

Cited by 51 publications

References 10 publications

Ontogeny of L-Glutamic Acid Decarboxylase and γ-Aminobutyric Acid Concentration in Human Kidney

Ontogeny of L-Glutamic Acid Decarboxylase and γ-Aminobutyric Acid Concentration in Human Kidney

Autoradiographic distribution of radioactivity from14C-GABA in the mouse

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

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