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

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. Field stimulation produced tetrodotoxin‐sensitive, frequency‐dependent, biphasic responses: rapid transient relaxation followed by a delayed inhibitory component. 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+ ‐dependent K + channels, or ADP β S, which desensitises P 2 y purinoceptors, reduced the slow relaxation to 2–8 Hz, without affecting that to 16–32 Hz or the fast relaxation. α ‐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. Relaxation to sodium nitroprusside was not affected by L ‐NAME, apamin or ADP β S, but was reduced by α ‐chymotrypsin or VIP6–28. Relaxation to VIP was abolished by α ‐chymotrypsin, antagonised by VIP6–28, but was not affected by L ‐NAME, apamin or ADP β S. Relaxation to ATP was abolished by apamin, antagonised by ADP β S, but was not affected by L ‐NAME or α ‐chymotrypsin. The present results suggest that NO is responsible for the rapid relaxation and partly for the slow relaxation. ATP is involved in the slow relaxation evoked by low frequencies of stimulation. VIP is responsible for the slow relaxation evoked by high frequencies of stimulation. The different neurotransmitters appear to work in parallel, although NO could serve also as a neuromodulator that facilitates release of VIP.British Journal of Pharmacology (2003) 140 , 431–437. doi: 10.1038/sj.bjp.0705431