Regulation of Vasoactive Intestinal Peptide and Substance P in the Human Pyloric Sphincter

Background/Aims: Brain-gut hormones (i.e., neuropeptides) such as vasoactive intestinal peptide (VIP) and substance P (SP) have been shown to exist in the enteric nervous system (ENS) of the pyloric sphincter (PS) in studies of immunohistochemistry. To clarify the role of neuropeptides in the ENS of the normal human PS, we investigated the enteric nerve responses to VIP and SP in normal human PS specimens in vitro. Methodology: Normal human PS specimens derived from 45 patients with early gastric cancer (35 men and 10 women aged from 44 to 65 years, average 57.4 years) were used. A total of 120 PS muscle strips were made from 45 PS. A mechano-graphic technique was used to evaluate in vitro muscle strip responses to VIP and SP before and after treatment with various autonomic nerve blockers. Results: Responses to VIP and SP after blockade of the adrenergic and cholinergic nerves: Relaxation was elicited by VIP in 41.7% at 1 x 10(-8), 62.5% at 1 x 10(-7), and 83.3% at 1 x 10(-6)g/ml. Differences were noted in the percentages showing relaxation between 1 x 10(-8) and 1 x 10(-7)g/ml, between 1 x 10(-8) and 1 x 10(-6)g/ml, and between 1 x 10(-7) and 1 x 10(-6)g/ml (p=0.0012, P < 0.0001, p=0.0002, respectively). Contraction was elicited by administration of by SP in 31.7% at 1 x 10(-8), 58.3% at 1 x 10(-7) and 79.2% at 1 x 10(-6)g/ml, respectively. Differences were noted in the percentages showing contraction between 1 x 10(-8) and 1 x 10(-7) g/ml, between 1 x 10(-8) and 1 x 10(-6) g/ml, and between 1 x 10(-7) and 1 x 10(-6) g/ml (p=0.0001, p < 0.0001, p=0.0004, respectively). VIP caused relaxation and substance P caused contraction of the PS in a concentration-dependent manner. Response to VIP and SP at 1 x 10(-6) g/ml after blockade of the ENS by tetrodotoxin (TTX): The relaxation to VIP and contraction to SP following administration of TTX were weaker than after blockade of the adrenergic and cholinergic nerves. In the normal human PS, VIP and SP may act both via NANC nerves and directly on the muscle strips. Conclusions: Relaxation reaction via VIP nerves and contraction via SP nerves might be involved in regulation of ENS in the normal human PS.