NANC inhibitory neurotransmission in mouse isolated stomach: involvement of nitric oxide, ATP and vasoactive intestinal polypeptide

Abstract

1 The neurotransmitters involved in NANC relaxation and their possible interactions were investigated in mouse isolated stomach, recording the motor responses as changes of endoluminal pressure from whole organ. 2 Field stimulation produced tetrodotoxin-sensitive, frequency-dependent, biphasic responses: rapid transient relaxation followed by a delayed inhibitory component. 3 The inhibitor of the synthesis of nitric oxide (NO), l-NAME, abolished the rapid relaxation and significantly reduced the slow relaxation. Apamin, blocker of Ca 2 þ -dependent K þ channels, or ADPbS, which desensitises P 2y purinoceptors, reduced the slow relaxation to 2 -8 Hz, without affecting that to 16 -32 Hz or the fast relaxation. a-Chymotrypsin or vasoactive intestinal polypeptide 6 -28 (VIP6 -28), antagonist of VIP receptors, failed to affect the fast component or the delayed relaxation to 2 -4 Hz, but antagonised the slow component to 8 -32 Hz.

Glucagon-like peptide-2 relaxes mouse stomach through vasoactive intestinal peptide release

“…The concentrations of the inhibitors used were determined from previous experiments, where they have been shown to be effective in mouse stomach (15) or from literature. These agents were added to the perfusing solution at least 30 min before the peptide was tested.…”

“…Whole stomach was used to examine the muscle function under conditions where the influence of external factors is removed, but the muscle performs in a manner analogous to its in vivo capacity and is able to relax in absence of contractile agents (15,16). In addition, experiments using circular muscular strips obtained from gastric fundus and antrum were performed to clarify the regional activity of GLP-2.…”

Deficiency of intramuscular ICC increases fundic muscle excitability but does not impede nitrergic innervation

“…2, A and C) and was in part apamin sensitive (Fig. 2, A and C), likely mediated by ATP (7,10). When fundic muscle preparations from the Ws/Ws rat were studied under identical conditions, usually no reduction in tone was observed (Fig.…”

Carbon monoxide mediates vasoactive intestinal polypeptide-associated nonadrenergic/noncholinergic neurotransmission

“…1). In other studies, we have observed HO2 and nNOS predominantly in the myenteric plexus throughout the gastrointestinal pathway (13,41). The similarity of VIP, nNOS, and HO2 localizations in mouse IAS to localizations throughout the gastrointestinal tract (11)(12)(13) implies that VIP-NANC transmission at other sites involves similar mechanisms as are involved in IAS.…”

“…3). In contrast, VIP can stimulate nNOS activity in mouse gastric fundus (33,34,41) and airway smooth muscle (35) to mediate NANC relaxation. Why would NANC relaxation in the IAS be mediated primarily by CO, whereas NO and CO are coneurotransmitters in other intestinal segments?…”