Uptake and Autoreceptor-Controlled Release of [&lt;sup&gt;3&lt;/sup&gt;H]-GABA by the Hypothalamic Median Eminence and Pituitary Neurointermediate Lobe

Anderson, Richard C. E.; Mitchell, Rory

doi:10.1159/000124452

Cited by 20 publications

(9 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results show that the anterior pituitary gland can accumulate 3H-GABA in a temperature-and sodiumdependent manner, and this was similar to the GABA uptake by other tissues [12,14,17,18]. Kinetic analysis indicates that GABA is transported by a saturable uptake process.…”

Section: Discussionsupporting

confidence: 70%

GABA Transport and Subcellular Distribution in the Rat Anterior Pituitary Gland

Duvilanski

Seilicovich²,

Debéljuk³

et al. 1994

Neuroendocrinology

View full text Add to dashboard Cite

In this investigation we have studied the uptake of gamma aminobutyric acid (GABA) into anterior pituitary slices. Tissue:medium ratios of about 45:1 were obtained after a 30-min incubation. The process responsible for ³H-GABA uptake was temperature-sensitive and sodium-dependent. The kinetic constants of saturable GABA transport were: K_m 4.141 µM and V_max 0.973 pmol/min/mg protein, at 25 °C. The incorporation of GABA into anterior pituitary was inhibited by specific inhibitors of neuronal and/or glial uptake. The subcellular distribution of GABA was investigated by continuous sucrose density gradients and differential centrifugation. Most of the endogenous and labelled GABA was present in the soluble fraction. However, a small part of GABA was found in the particulate fraction. These observations indicate that the anterior pituitary gland is able to concentrate GABA which interacts with intracellular particles.

show abstract

Section: Discussionsupporting

confidence: 70%

GABA Transport and Subcellular Distribution in the Rat Anterior Pituitary Gland

Duvilanski

Seilicovich²,

Debéljuk³

et al. 1994

Neuroendocrinology

View full text Add to dashboard Cite

show abstract

“…Recent morphological investigations have demonstrated the presence of a dense network of GABAergic fibres which closely surround the CRF-41 neurons in the paraventricular nucleus (6, 7), while ultrastructural observations have shown that nerve endings containing glutamic acid decarboxylase, the enzyme involved in GABA synthesis, make synaptic contacts on CRF-41 neurons (6). Furthermore, GABA receptors appear to be present on nerve terminals within the median eminence (20). Thus, a dual site of action of GABA can be tentatively suggested, with GABA acting both on axon terminals as well as on cell bodies.…”

Section: Discussionmentioning

confidence: 99%

Gamma‐Aminobutyric Acid Modulation of Corticotrophin‐Releasing Factor‐41 Secretion from the Rat Hypothalamus in vitro

Tsagarakis

Rees

Besser

et al. 1990

J Neuroendocrinology

View full text Add to dashboard Cite

There is increasing evidence for a centrally mediated inhibitory effect of the amino-acid neurotransmitter y-aminobutyric acid (GABA) on the hypothalamo-pituitary-adrenal axis. In the present study, the direct effect of GABA in modulating the release of the 41-residue corticotrophin-releasing factor (CRF-41), the major CRF identified so far, was investigated in acute hypothalamic explants by utilizing previously validated incubation and assay techniques. While GABA (lo-' to M) had no effect on basal CRF-41 release (P>0.05), it significantly suppressed K' (28 mM)-stimulated release in a dose-dependent manner (PiO.01). A similar inhibitory effect was observed with the GABA, agonist muscimol to M). Noradrenaline M)-induced CRF-41 release was also significantly inhibited by GABA 10-M. The inhibitory effect of GABA on K+-stimulated CRF-41 secretion was completely.reversed by the GABA antagonists bicuculline and picrotoxin M) in a dose-dependent fashion. Both bicuculline and picrotoxin stimulated basal and K + (28 mM)-stimulated CRF-41 release, indicating the presence of tonic inhibition by endogenous GABA in the basal state. Finally, GABA M was able to significantly inhibit the stimulated release of CRF-41 from the isolated median eminence.In summary, the present data provide strong evidence that GABA-induced inhibition of the hypothalamo-pituitary-adrenal axis is mediated, at least in part, through an inhibitory action on CRF-41 secretion. It is likely that these GABA receptors are located directly on CRF-41 neurons, probably on nerve terminals in the median eminence. toIn recent years progress in our knowledge on the neurotransmitter control of the pituitary-adrenal axis has suggested an important role for y-aminobutyric acid (GABA) on adrenocorticotrophin (ACTH) secretion. In particular, studies both in vivo (1-3) and in vitro (4, 5), the latter measuring the release of bioactive corticotrophin-releasing factor(s) (CRF), have demonstrated an inhibitory role for GABA in the regulation of ACTH and glucocorticoid secretion, and have provided good evidence for a central site of action (4, 5). Furthermore, recent immunohistochemical data have clearly shown a close relationship between hypothalamic GABAergic neurons and neurons containing the 41-residue C R F (CRF-41) (6, 7). However, there are currently few data on the role of GABA in regulating the rcleasc of CRF-41, although a recent study has demonstrated inhibition of acetylcholine-stimulated release by GABA at a single dose (8, 9). In the present study, therefore, we have investigated the direct effect of GABA in modulating the release of CRF-41 from acute hypothalamic explants in vitro, using previously validated incubation and assay techniques (10). ResultsAs shown in Fig. 1, GABA in the concentration range lo-' to 10-M significantly suppressed KC1 (28 mM)-stimulated release in a dose-dependent manner (P < 0.01); this was significantly different to the control incubation at both M and M, but not at M. GABA lo-' M was without effect. The GABA, receptor ag...

show abstract

“…The neurochemical evidence for a role of GABA in the regulation of the secretory activity of melanotrophs includes: (1) immunoreactive glutamic acid decarboxylase (GAD), a selective marker for GABAergic neurones, has been detected in synapselike junctions around secretory cells of the rat PI; (2) mechanical or electrolytic lesioning of the pituitary stalk abolishes GAD immunoreactivity indicating that it arises, not from local GABAergic neurones, but from descending pathways originating, most likely, in the hypothalamus (Oertel et al, 1982;Vincent et al, 1982); (3) Anderson & Mitchell (1986) have demonstrated the presence of GABA binding, uptake, and calcium-dependent release in the rat neurointermediate lobe; and, (4) GABA has been shown briefly to stimulate and then inhibit the release of a-MSH from dispersed melanotrophs (Tomiko et al, 1983). From the observation that the barium-stimulated release of x-MSH is selectively enhanced by isoguvacine, a GABAA receptor agonist, and reduced by baclofen, a GABAI receptor agonist (Demeneix et al, 1984; it has been inferred that the stimulatory and inhibitory actions of GABA itself reflect the consequences of GABAA and GABAB receptor occupation, respectively.…”

Section: Introductionmentioning

confidence: 99%

A patch clamp study of γ‐aminobutryic acid (GABA)‐induced macroscopic currents in rat melanotrophs in cell culture

Kehl

Hughes

McBurney

1987

British J Pharmacology

View full text Add to dashboard Cite

1The macroscopic currents induced in cultured rat melanotrophs by exogenous y-aminobutyric acid (GABA) were analysed using the patch clamp recording technique. 2 Using various concentrations of intra-and extracellular chloride it was demonstrated that the conductance activated by GABA was chloride selective. Since these currents were blocked with bicuculline and enhanced with chlordiazepoxide the involvement of GABAA receptors similar to those in the CNS is indicated. 3 When chloride was symmetrically distributed across the membrane the voltage/current relationship was linear; pronounced rectification of GABA mediated currents was evident when there was an asymmetrical distribution of chloride. 4 With concentrations of GABA greater than 1O 1M a fading of the current was seen during prolonged (5-10 s) applications. This effect appeared to be due to a decline of conductance rather than a shift of the chloride equilibrium potential. 5 Values for the Hill coefficient derived from dose-response curves suggested that the binding of 2 molecules of GABA to the receptor is required for the activation of the chloride channel. 6 There was no indication of a direct, GABAB receptor-mediated change of conductance.

show abstract

Uptake and Autoreceptor-Controlled Release of [<sup>3</sup>H]-GABA by the Hypothalamic Median Eminence and Pituitary Neurointermediate Lobe

Cited by 20 publications

References 3 publications

GABA Transport and Subcellular Distribution in the Rat Anterior Pituitary Gland

GABA Transport and Subcellular Distribution in the Rat Anterior Pituitary Gland

Gamma‐Aminobutyric Acid Modulation of Corticotrophin‐Releasing Factor‐41 Secretion from the Rat Hypothalamus in vitro

A patch clamp study of γ‐aminobutryic acid (GABA)‐induced macroscopic currents in rat melanotrophs in cell culture

Contact Info

Product

Resources

About