DMPP causes relaxation of rat distal colon by a purinergic and a nitrergic mechanism

The non-adrenergic relaxation of carbachol precontracted longitudinal muscle of the rat distal colon was investigated. Intrinsic nerves were activated by the nicotinic, ganglionic receptor agonist, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP). DMPP at 1 and 4 microM caused a relaxation that was markedly antagonized by the nerve blocker tetrodotoxin (1 microM) or the nicotinic receptor antagonist, hexamethonium (1 mM). The response to DMPP was significantly antagonized by apamin (an inhibitor of ATP-sensitive K+-channels), by reactive blue 2 (a blocker of P2y purinoceptors) and by an inhibitor of nitric oxide (NO)-synthase (N(G)-nitro-L-arginine, L-NNA). The combined treatment with reactive blue 2 and L-NNA reduced the relaxatory response to 1 microM DMPP by 77 +/- 8% and to 4 microM DMPP by 58 +/- 4% of control, but left a residual component. Our results indicate that ATP and NO, together with at least one additional (hitherto unidentified) substance may be inhibitory neurotransmitters in rat distal colon.