Gamma-Aminobutyric Acid Modulation of Corticotrophin-Releasing Factor-41 Secretion from the Rat Hypothalamus in vitro.
Abstract 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-releasi...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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1990
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| _version_ | 1797099821095452672 |
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| author | Tsagarakis, S Rees, L Besser, G Grossman, A |
| author_facet | Tsagarakis, S Rees, L Besser, G Grossman, A |
| author_sort | Tsagarakis, S |
| collection | OXFORD |
| description | Abstract 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 (10(-7)'to 10(-5) 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 (P < 0.01). A similar inhibitory effect was observed with the GABA agonist muscimol (10(-7) to 10(-5) M). Noradrenaline (10(-6) M) -induced CRF-41 release was also significantly inhibited by GABA 10(-6) M. The inhibitory effect of GABA on K(+)-stimulated CRF-41 secretion was completely. reversed by the GABA antagonists bicuculline and picrotoxin (10(-6) to 10(-5) 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 10(-5) 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. |
| first_indexed | 2024-03-07T05:29:03Z |
| format | Journal article |
| id | oxford-uuid:e191d882-1067-41f7-a6a0-7062e5da1c50 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:29:03Z |
| publishDate | 1990 |
| record_format | dspace |
| spelling | oxford-uuid:e191d882-1067-41f7-a6a0-7062e5da1c502022-03-27T09:55:27ZGamma-Aminobutyric Acid Modulation of Corticotrophin-Releasing Factor-41 Secretion from the Rat Hypothalamus in vitro.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e191d882-1067-41f7-a6a0-7062e5da1c50EnglishSymplectic Elements at Oxford1990Tsagarakis, SRees, LBesser, GGrossman, AAbstract 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 (10(-7)'to 10(-5) 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 (P < 0.01). A similar inhibitory effect was observed with the GABA agonist muscimol (10(-7) to 10(-5) M). Noradrenaline (10(-6) M) -induced CRF-41 release was also significantly inhibited by GABA 10(-6) M. The inhibitory effect of GABA on K(+)-stimulated CRF-41 secretion was completely. reversed by the GABA antagonists bicuculline and picrotoxin (10(-6) to 10(-5) 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 10(-5) 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. |
| spellingShingle | Tsagarakis, S Rees, L Besser, G Grossman, A Gamma-Aminobutyric Acid Modulation of Corticotrophin-Releasing Factor-41 Secretion from the Rat Hypothalamus in vitro. |
| title | Gamma-Aminobutyric Acid Modulation of Corticotrophin-Releasing Factor-41 Secretion from the Rat Hypothalamus in vitro. |
| title_full | Gamma-Aminobutyric Acid Modulation of Corticotrophin-Releasing Factor-41 Secretion from the Rat Hypothalamus in vitro. |
| title_fullStr | Gamma-Aminobutyric Acid Modulation of Corticotrophin-Releasing Factor-41 Secretion from the Rat Hypothalamus in vitro. |
| title_full_unstemmed | Gamma-Aminobutyric Acid Modulation of Corticotrophin-Releasing Factor-41 Secretion from the Rat Hypothalamus in vitro. |
| title_short | Gamma-Aminobutyric Acid Modulation of Corticotrophin-Releasing Factor-41 Secretion from the Rat Hypothalamus in vitro. |
| title_sort | gamma aminobutyric acid modulation of corticotrophin releasing factor 41 secretion from the rat hypothalamus in vitro |
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