The purpose of this study was to determine the interactions between bombesin and substance P at the feline lower esophageal sphincter (LES). Intraluminal pressures were recorded using a fixed, perfused catheter assembly. Myoelectrical activity was recorded using bipolar Ag-AgCl serosal electrodes. Bombesin, i.v., gave a dose-dependent increase in LES pressure and electronically counted spike activity. The threshold dose was 10-7 g/kg, while the maximal dose, 10-5 g/kg, increased LES pressure by 65.5±14.8 mmHg. The neuroantagonist, tetrodotoxin, decreased the LES response to bombesin by 74.1%±7.9% (P < 0.05), but had no significant effect on the LES response to substance P. The sphincteric response to bombesin was not inhibited by bilateral cervical vagotomy, atropine, propranolol, or phentolamine (P < 0.10). Bombesin tachyphylaxis abolished the LES response to bombesin but had no effect on the response to substance P. Conversely, substance P tachyphylaxis completely abolished the LES response to bombesin (P < 0.001). The substance P antagonist [D-Pro2, D-Trp7,9]substance P also significantly inhibited the LES response to bombesin (P < 0.05). Acidification of the distal esophagus with 2.0 ml of 0.1 N HCl increased LES pressure by 32.5 ± 5.2 mmHg (P < 0.02). The LES response to acid was inhibited by bombesin tachyphylaxis (maximal pressure response, 4.7 ± 2.1 mmHg, P < 0.01 compared with control acid response). The tachyphylaxis techniques were specific for the peptides giving no effect on the LES responses to phenylephrine, bethanechol, or pentagastrin. We drew the following conclusions: (a) bombesin increased feline LES pressure via nonvagal neural pathways that were insensitive to adrenergic or cholinergic antagonists; (b) bombesin may be involved in the enteric pathways that mediate the feline LES response to distal esophageal acidification; and (c) substance P mediates the effect of bombesin at the LES and is a neurotransmitter in the LES response to acidification.
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