This might help a little.
Effects of GABA on circular smooth muscle spontaneous activities of rat distal colon
S Bayer, F Crenner, D Aunis, F Angel ,
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INSERM Unité 338. Groupe de Neurogastroentérologie. Pavillon Poincaré. Hôpital Civil. 67000 Strasbourg, France
Received 23 July 2001; Accepted 1 February 2002. Available online 22 May 2002.
Abstract
GABAergic regulation of intestinal motility through the modulation of non-adrenergic non-cholinergic (NANC) neurons remains poorly understood especially in rat colon where very few studies have been undertaken. Thperefore, the effects of GABA on circular preparations of rat distal colon were investigated using classical organ bath chambers to record spontaneous mechanical activities (SMA). SMA was characterized by the occurrence of rhythmic phasic contractions (type-I) or by spontaneously occurring large contractions superimposed on small rhythmic contractions (type-II). In the presence of atropine and guanethidine (NANC conditions), these large contractions were inhibited by bicuculline, a GABAA-receptor antagonist as well as by TTX, L-NAME and apamin together, or L 732-138, a NK1-receptor antagonist. In NANC conditions, GABA induced a transient monophasic relaxation or a biphasic effect characterized by a relaxation followed by a tonic contraction in both type-I and -II preparations. Both the inhibitory and excitatory effects of GABA were blocked by TTX and L-NAME + apamin; the GABA-induced contraction was also sensitive to L 732-138. The responses to GABA were mimicked by the GABAA-receptor agonist, muscimol, whereas baclofen and CACA, respectively GABAB and GABAC-receptors agonists showed no effect. These results demonstrated that only GABAA-receptors seem to be involved in the regulation of SMA in rat distal colon in NANC conditions. Release of NANC inhibitory transmitter (NO and probably ATP) and NANC excitatory transmitter (maybe substance P) might be involved.
Keywords: GABA; NANC neurons; Smooth muscle; Motility; Colon; Rat
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http://www.frontiersin.org/gastrointestinal_pharmacology/10.3389/fphar.2010.00124/full
summary of above
γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the body and hence GABA-mediated neurotransmission regulates many physiological functions, including those in the gastrointestinal (GI) tract. GABA is located throughout the GI tract and is found in enteric nerves as well as in endocrine-like cells, implicating GABA as both a neurotransmitter and an endocrine mediator influencing GI function. GABA mediates its effects via GABA receptors which are either ionotropic GABAA or metabotropic GABAB. The latter which respond to the agonist baclofen have been least characterized, however accumulating data suggest that they play a key role in GI function in health and disease. Like GABA, GABAB receptors have been detected throughout the gut of several species in the enteric nervous system, muscle, epithelial layers as well as on endocrine-like cells. Such widespread distribution of this metabotropic GABA receptor is consistent with its significant modulatory role over intestinal motility, gastric emptying, gastric acid secretion, transient lower esophageal sphincter relaxation and visceral sensation of painful colonic stimuli. More intriguing findings, the mechanisms underlying which have yet to be determined, suggest GABAB receptors inhibit GI carcinogenesis and tumor growth. Therefore, the diversity of GI functions regulated by GABAB receptors makes it a potentially useful target in the treatment of several GI disorders. In light of the development of novel compounds such as peripherally acting GABAB receptor agonists, positive allosteric modulators of the GABAB receptor and GABA producing enteric bacteria, we review and summarize current knowledge on the function of GABAB receptors within the GI tract.
Full article is long but conclusion:
Summary and Conclusions
The diversity of GI functions regulated by GABAB receptors make it a potentially useful target in the treatment of several GI disorders, but may also limit its therapeutic application due to off target side effects, both in the GI tract and centrally. For example GERD patients and healthy volunteers treated with baclofen reported adverse effects of a neurological nature that included drowsiness and dizziness (Lidums et al., 2000; van Herwaarden et al., 2002; Ciccaglione and Marzio, 2003). However, the development of peripherally acting compounds such as lesogaberan, which by virtue of its affinity for GABA carriers (Lehmann et al., 2009) limits its effects at central GABAB receptors, may well overcome the disadvantages associated with traditional GABAB agonists. Lesogaberan, like baclofen, displays efficacy in the treatment of GERD (Boeckxstaens et al., 2010a,b), but has yet to be tested in other GI disorders where targeting peripheral GABAB receptors could also be therapeutically useful, i.e., in motility disorders. Furthermore, over the last several years a number of positive allosteric modulators of the GABAB receptor have been developed (Urwyler et al., 2001, 2003; Malherbe et al., 2008). One of which, CGP7930, reduces the visceral pain response induced by CRD (Brusberg et al., 2009) and may therefore be therapeutically useful in the treatment of functional bowel disorders such as irritable bowel syndrome where visceral pain is a predominant and debilitating symptom. These modulators offer advantages over traditional GABAB agonists, such as baclofen, as their actions occur following enhancement of endogenous GABA release or transmission, thereby limiting the side-effects that are normally associated with traditional agonist treatment. More novel strategies for delivering GABA to the GI tract in the form of engineered bacteria, such as GAD transfected Bifidobacterium longum (Park et al., 2005), or the development of GABA containing functional foods (Minervini et al., 2009) are in their infancy, but may offer potential in treating GI conditions that are GABA or GABAB receptor-sensitive.