GABAergic inhibition of nitric oxide-mediated relaxation of guinea-pig ileum

Abstract

The effects of GABA receptor agonists were investigated on guinea-pig isolated ileum longitudinal muscle with intact myenteric plexus. Electrical field stimulation (1 Hz, 10 s) of the histamine (1 microM)-precontracted preparation caused a contraction followed by a relaxation. Relaxations were inhibited by L-N(G)-nitroarginine (L-NA; EC50 3 microM) in a concentration-dependent manner. The inhibitory action of 10 microM L-NA was blocked by 10 microM L-arginine but not by D-arginine, which indicates that the relaxation was largely mediated by endogenous nitric oxide (NO). Tetrodotoxin (1 microM) reduced the relaxation only by about 50%. GABA and the GABA(B) agonist, baclofen, inhibited the field stimulation-induced longitudinal muscle relaxation in a concentration-dependent manner. The GABA(B) receptor antagonist, saclofen (10 microM), antagonised the effect of baclofen (apparent pA2 of saclofen: 5.6). Muscimol (10 microM) similarly inhibited the relaxation, and this inhibition was prevented by bicuculline (1 microM). It is concluded that nitrergic nerves of the guinea-pig myenteric plexus are endowed with GABA(A) and GABA(B) receptors which mediate inhibition of NO release.

Furosemide suppresses ileal and colonic contractility via interactions with GABA‐A receptor in mice

“…Inhibition of the ionotropic GABA‐A receptor may work on the enteric cholinergic excitatory, leading to inhibition of the release of Ach and/or stimulation of the non‐adrenergic non‐cholinergic (NANC) inhibitory motor neuron. Consequently it enhanced the release of nitric oxide (NO), and led to relaxation of the ileal longitudinal smooth muscle. However, the inhibition of the proximal colonic smooth muscle contraction was greater when adding furosemide following muscimol/atropine (Figures B and B).…”

“…26 However, in this experiment, muscimol could not increase the contraction after furosemide addition. These Consequently it enhanced the release of nitric oxide (NO), 20,[27][28][29] and led to relaxation of the ileal longitudinal smooth muscle. However, the inhibition of the proximal colonic smooth muscle contraction was greater when adding furosemide following muscimol/atropine ( Figures 5B and 7B).…”

Vagal neurotransmission to the ferret lower oesophageal sphincter: inhibition via GABAB receptors

“…Immunohistochemical studies have suggested that GABA, colocalized with nitric oxide synthase in motorneurones of the guinea‐pig ileum, may also regulate nitric oxide release ( Williamson et al ., 1996 ). Functional studies suggest that both GABA A and GABA B receptors have the capacity to inhibit NO release in myenteric neurones of the guinea‐pig ileum ( Kilbinger et al ., 1999 ). Presynaptic inhibition of acetylcholine release via GABA B receptors occurs at lumbar preganglionic splanchnic nerves synapsing within the inferior mesenteric ganglion of the guinea‐pig ( Parkman et al ., 1993 ).…”

Gastroesophageal reflux disease and baclofen: Is there a light at the end of the tunnel?

“…GABA B receptors are found in the myenteric plexus of the stomach and esophagus, but their physiologic significance is essentially unstudied [18]. In the ileum, baclofen inhibits smooth muscle relaxation caused by stimulation of nitrergic myenteric nerves [25]. Whether a similar mechanism functions in the LES is yet to be explored.…”