4-Aminobutanoic acid

Effect of gamma-aminobutyric acid on digestive enzymes, absorption function, and immune function of intestinal mucosa in heat-stressed chicken.[Pubmed:25085934]

Poult Sci. 2014 Oct;93(10):2490-500.

To explore the effect of dietary gamma-aminobutyric acid (GABA) on digestive enzyme activity, absorption function and immune function of intestinal mucosa in heat-stressed Wenchang chicken were studied. One-day-old male Wenchang chickens were randomly divided into a control group (CK), heat stress group (HS), and GABA+HS group. The chickens from the GABA+HS group were administered with 0.2 mL of GABA solution daily. Chickens from HS and GABA+HS groups were subjected to heat stress treatment at 40 +/- 0.5 degrees C for 2 h during 1300 to 1500 h every day. Blood was drawn and 0.5 cm-long duodenum, jejunum, and ileum were collected from the chickens on d 3, 5, 7, 9, 12, and 15. Results showed that the activity of Ca(2)(+)-Mg(2)(+)-adenosine triphosphatase (ATPase), Na(+)-K(+)-ATPase, maltase, sucrase, and alkaline phosphatase, the contents of secretory IgA, glutathione, and d-xylose, and the number of lymphocytes in HS group were significantly lower than those in the CK group. Among them, some were rescued after the treatment of GABA as the time extension. For maltase, d-xylose, alkaline phosphatase, and Na(+)-K(+)-ATPase, it required 5 to 7 d for achieving the significant effect. For sucrase, 12 d for the alleviation effect was required. In the case of other parameters, no alleviation was observed during the whole period of the study. We have concluded that HS can inhibit the activity of digestive enzymes and reduce absorption and immune functions of intestinal mucosa. gamma-Aminobutyric acid can effectively alleviate these inhibitory effects.

Anxiety in major depression and cerebrospinal fluid free gamma-aminobutyric acid.[Pubmed:24865448]

Depress Anxiety. 2014 Oct;31(10):814-21.

BACKGROUND: Low gamma-aminobutyric acid (GABA) is implicated in both anxiety and depression pathophysiology. They are often comorbid, but most clinical studies have not examined these relationships separately. We investigated the relationship of cerebrospinal fluid (CSF) free GABA to the anxiety and depression components of a major depressive episode (MDE) and to monoamine systems. METHODS AND MATERIALS: Patients with a DSM-IV major depressive episode (N = 167: 130 major depressive disorder; 37 bipolar disorder) and healthy volunteers (N = 38) had CSF free GABA measured by gas chromatography mass spectroscopy. Monoamine metabolites were assayed by high performance liquid chromatography. Symptomatology was assessed by Hamilton depression rating scale. RESULTS: Psychic anxiety severity increased with age and correlated with lower CSF free GABA, controlling for age. CSF free GABA declined with age but was not related to depression severity. Other monoamine metabolites correlated positively with CSF GABA but not with psychic anxiety or depression severity. CSF free GABA was lower in MDD compared with bipolar disorder and healthy volunteers. GABA levels did not differ based on a suicide attempt history in mood disorders. Recent exposure to benzodiazepines, but not alcohol or past alcoholism, was associated with a statistical trend for more severe anxiety and lower CSF GABA. CONCLUSIONS: Lower CSF GABA may explain increasing severity of psychic anxiety in major depression with increasing age. This relationship is not seen with monoamine metabolites, suggesting treatments targeting the GABAergic system should be evaluated in treatment-resistant anxious major depression and in older patients.

GABAc receptors: relatively simple transmitter -gated ion channels?[Pubmed:8885697]

Trends Pharmacol Sci. 1996 Sep;17(9):319-23.

The inhibitory neurotransmitter, GABA, activates a variety of receptors in all areas of the CNS. Two major subtypes of GABA receptors are well known: (1) GABAA receptors are ligand-gated Cl- channels that consist of a heteromeric mixture of protein subunits forming a pentameric structure, and (2) GABAB receptors couple to Ca2+ and K+ channels via G proteins and second messengers. Here, Graham Johnston discusses evidence for a third major subclass of GABA receptors. GABAC receptors appear to be relatively simple ligand-gated Cl- channels with a distinctive pharmacology, in that they are not blocked by bicuculline and not modulated by barbiturates, benzodiazepines or neuroactive steroids. Compared with GABAA receptors, GABAC receptors are activated at lower concentrations of GABA and are less liable to desensitization. In addition, their channels open for a longer time. The pharmacology of these novel subtypes of GABA receptors may yield important therapeutic agents.

GABA and its receptors in the spinal cord.[Pubmed:9014500]

Trends Pharmacol Sci. 1996 Dec;17(12):457-62.

The importance of the inhibitory neurotransmitter, GABA, within higher centres of the mammalian brain is unquestionable. However, its role within the spinal cord is of equal significance. There have been numerous studies over the past two decades that have established GABA as a neurotransmitter at both post- and presynaptic sites in the cord. Here, Marzia Malcangio and Norman Bowery review the current status of GABA in relation to nociception and skeletal muscle tone, and indicate that its contribution to spinal cord function should not be overlooked.

GABA: a dominant neurotransmitter in the hypothalamus.[Pubmed:2081813]

J Comp Neurol. 1990 Dec 22;302(4):1019-37.

To study the organization and distribution of the inhibitory amino acid neurotransmitter GABA in the medial hypothalamus, we used a postembedding immunocytochemical approach with colloidal gold. Quantitative analysis showed that half (49%) of all synapsing boutons studied were immunoreactive for GABA, based on immunogold staining of the suprachiasmatic, arcuate, supraoptic, and paraventricular nuclei. This was corroborated with pre-embedding peroxidase immunostaining with antisera against glutamate decarboxylase, the GABA synthetic enzyme. These data suggest that GABA is the numerically dominant neurotransmitter in the hypothalamus, and emphasize the importance of inhibitory circuits in the hypothalamus. Serial ultrathin sections were used to reconstruct GABA immunoreactive boutons and axons in three dimensions. With this type of analysis we found less morphological heterogeneity between GABA immunoreactive boutons than with single ultrathin sections. Single sections sometimes showed boutons containing only small clear vesicles, and other with both clear vesicles and small dense core vesicles. However, with serial sections through individual boutons, dense core vesicles were consistently found at the periphery of the pre-synaptic GABA immunoreactive boutons, suggesting probable co-localization of GABA with unidentified peptides in most if not all boutons throughout the hypothalamus. A positive correlation was found between the density of small clear vesicles and the intensity of immunostaining with colloidal gold particles. GABA immunoreactive axons generally made symmetrical type synaptic specializations, although a small percentage made strongly asymmetrical synaptic specializations. Vesicles in GABA immunoreactive boutons were slightly smaller than those in non-reactive boutons. Synaptic efficacy is related to the position of the synapse on the post-synaptic neuron. While the majority of GABA immunoreactive axons made synaptic contact with dendrites, the distribution of GABA immunoreactive synapses on somata and dendrites was the same as would be expected from a random distribution of all boutons. No preferential innervation of cell bodies by GABA immunoreactive terminals was found. Serial ultrathin sections showed that a GABA immunoreactive axon would sometimes make repeated synaptic contacts with a single postsynaptic neuron, indicating a high degree of direct control by the presynaptic GABAergic cell. Other immunoreactive axons made synaptic contact with a number of adjacent dendrites and cells, suggesting a role for GABA in synchronizing the activity of hypothalamic neurons. Based on the density of immunogold particles per unit area, varying concentrations of immunoreactive GABA were found in different presynaptic boutons in the hypothalamus.

γ-Aminobutyric acid (4-Aminobutyric acid) is a major inhibitory neurotransmitter in the adult mammalian brain, binding to the ionotropic GABA receptors (GABAA receptors) and metabotropic receptors (GABAB receptors).

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