ISSN:
1365-2826
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1365-2826.1990.tb00854.x
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