<atl>Tachykinin-stimulated small bowel myoelectric pattern: sensitization by NO inhibition, reversal by neurokinin receptor blockade

Tachykinins stimulate motility whereas NO inhibits motility in the gastrointestinal tract. Aim: To investigate if inhibition of NO production sensitizes myoelectric activity to subthreshold doses of tachykinins in the small intestine of awake rats. Methods: Rats were supplied with a venous catheter and bipolar electrodes at 5, 15 and 25 cm distal to pylorus for electromyography of small intestine. The motor responses were evaluated using pattern recognition. Substance P and neurokinin A dose-dependently stimulated gut motility, with neurokinin A being more potent than substance P. Therefore, neurokinin A was chosen and administered under baseline conditions and 45–60 min after Nω-nitro-l-arginine (l-NNA) 1 mg kg−1, with or without pretreatment with l-arginine 300 mg kg−1. In addition, myoelectric activity effects of neurokinin A in conjunction with l-NNA were studied before and after administration of the tachykinin receptor antagonists, SR140333 (NK1), SR48968 (NK2) and SR142801 (NK3), each at 2.5 mg kg−1. Results: Dose-finding studies verified 10 pmol kg−1 min−1 to be the threshold dose at which NKA caused phase II-like activity in a low percentage of experiments (12%, n=41). This dose was therefore used in combination with l-NNA for sensitization experiments of gut myoelectric activity. In experiments where NKA-induced no response, pretreatment with l-NNA led to phase II-like activity in 9 of 18 (50%, p<0.05) experiments. Co-administration of SR140333 and SR48968 abolished this effect. Conclusion: NO counteracts the stimulatory effect of tachykinins on small bowel myoelectric activity in the rat. Inhibition of the l-arginine/NO pathway sensitizes the gut to tachykinin-stimulated motor activity. [Copyright &y& Elsevier]