PATTERN OF NONADRENERGIC, NONCHOLINERGIC RESPONSES DURING SHORT-LASTING OR LONG-LASTING ELECTRICAL-STIMULATION IN GUINEA-PIG ILEUM

1. The pattern of responses of longitudinally oriented guinea pig ileu m organ bath preparations was studied during short (1-5 sec) or long-l asting (20 sec) electrical field stimulation (EFS, 0.8 msec, 40 V, 1-2 0 Hz). 2, In the presence of phentolamine (5 mu M), propranolol (5 mu M), and atropine (3 mu M), the EFS elicited nonadrenergic, noncholiner gic (NANC), tetrodotoxin (0.3 mu M)-sensitive responses. 3. The I-sec EFS evoked relaxation. The response to 5-sec EFS consisted of relaxati on followed by twitch, whereas relaxation, twitch and tonic contractio n characterized the NANC response to 20-sec EFS. The maximum relaxatio n was observed at 10-Hz short- or long-lasting EFS. 4. Both N-G-nitro- L-arginine (L-NNA, 0.1-0.5 mM) and apamin (1-5 mu M) concentration dep endently inhibited the relaxation of the NANC response to IO-Hz 20-sec EFS. During L-NNA treatment, the twitch and the tonic contractions we re increased. The inhibitory effect of L-NNA was reversed by L-arginin e (0.1-0.5 mM) but not by D-arginine. Sodium nitroprusside (1-10 mu M) was without effect. 5. AP 13.2 ACOH (0.1 mu M), a blocker of Substanc e P receptors, inhibited the twitch and the tonic contractions. The co ntractions were decreased after desensitization of purinoceptors by AT P and in the presence of the GABAA receptor antagonist bicuculline (30 mu M). 6. Depending on the EFS duration, a subsequent occurrence of r elaxation and contractions characterized the NANC responses. It seems that relaxation is mediated by nitric oxide whereas Substance P and AT P are involved in the maintenance of the twitch and the tonic contract ions. Nitric oxide appears to exert an inhibitory effect on the excita tory transmitters, whereas purinergic mechanism(s) could modulate the nitric oxide-dependent relaxation. GEN PHARMAC 29;2:233-237, 1997. (C) 1997 Elsevier Science Inc.