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All the epithelia lining the gastrointestinal (GI) tract, including that of the esophagus, exhibit a transmucosal electrical potential difference (PD). The luminal surface of the GI mucosa is indeed electrically negative when compared with the serosal one. Although it was initially felt that the body of the esophagus exhibits a PD near 0 or slightly positive, recent studies, using parenteral reference electrodes, have shown a negative PD of around -15 mV. Measurement of esophageal PD has been mainly used to locate both the lower and the upper esophageal sphincters but very rarely to evaluate esophageal mucosal integrity in clinical settings, most probably due to the difficulties encountered during measurement of mucosal PD. Reliable techniques to measure esophageal PD simultaneously with esophageal pressure or mucosal pH are now available. Application of these recently developed methodologies showed that measurement of esophageal PD during either manometry or endoscopy provides meaningful information about mucosal integrity. Indeed, tissue injury, either neoplastic or inflammatory, usually results in a less negative PD. In contrast, an abnormally high negative PD is very often observed in patients with columnar-lined lower esophagus. In patients with microscopic reflux esophagitis, PD exhibits less negative values which are significantly correlated with the degree of the mucosal damage. Normalization of the altered PD after either medical or surgical treatment makes it an additional parameter to evaluate the effect of a given therapy.

SUMMARY The effect of bombesin on insulin and gastrin response to a standard labelled meal was studied in eight healthy male volunteers. The gastric emptying of solids was simultaneously evaluated. During intravenous infusion of the peptide (5 ng/kg/min) the insulin release after eating was greatly reduced whereas food stimulated gastrin release was significantly enhanced. Both effects of bombesin are likely to be connected with the marked inhibition of gastric emptying induced by the peptide.Bombesin is a frog skin tetradecapeptide which has been found to have similar immunologically charactensed counterparts in mammalian gut. 1-3 An heptacosapeptide has been isolated from porcine non-antral gastric tissue: the so called gastrin releasing peptide (GRP).4 The homology of its C-terminal decapeptide with C-terminal decapeptide of bombesin is impressive. As a consequence, both these peptides have the same spectrum of biological actions, although some qualitative differences have been reported.Many radioimmunological and immunocytochemical observations indicate that bombesin like peptides are confined to neurones and fibres of the intramural plexus of the gUt.6 7 As a consequence, they have been put forward as putative neurotransmitters in mammalian gut.Bombesin was shown to be a potent and polivalent releaser of several gastrointestinal hormones both in animals and humans.8 Its gastrin releasing effect, first demonstrated in dogs, was repeatedly confirmed in other animal species including man.8 10 On the contrary, results concerning its effect on insulin secretion have been contradictory. A stimulation of insulin release was observed in dogs," cats,12 and man13 14 whereas an inhibition was reported in rats.'5 In vitro studies have provided conflicting results, as well. In fact, whereas bombesin stimulates insulin secretion in isolated and perfused pancreas from dogs'6 and rats17 it inhibits the hormone release from isolated rat pancreatic islets.'8 The recent discovery of bombesin like immunoreactivity in the human pancreas13 suggests that this peptide may also affect human pancreatic secretion. Therefore we decided to study in man its effect on insulin response to food. Because bombesin was shown to affect gastric emptying,19 the effect of the peptide on emptying rate was simultaneously evaluated.Preliminary results of the present investigation have been presented at the Italian Society of Gastroenterology (June 1981) and appeared in abstract form. Methods

The effect of bombesin on basal and glucose-stimulated insulin release was studied in male healthy volunteers. Glucose was administered by oral, intravenous or intraduodenal route during saline or bombesin infusion (5 ng/kg/min for 60 min). The peptide had no significant effect on basal levels of glucose and insulin. However, during its administration, the insulin response and the expected rise in blood glucose after oral glucose load (50 g) were strongly inhibited, and the gastric emptying of liquids was significantly delayed. On the contrary, the insulin response to intravenous glucose (20 g) was significantly increased by bombesin without changes in plasma glucose levels. Finally, when glucose was infused into the duodenum, thus bypassing the stomach, the insulin response was significantly increased by the peptide. In this case, too, plasma glucose levels after glucose load were virtually identical during either bombesin or saline infusion. These data clearly demonstrate that the direct effect of bombesin on insulin release is stimulatory and suggest that the inhibitory effect observed after oral glucose is connected with the action of the peptide on gastric emptying, the delay of which slows the entry of glucose into the small bowel.

Bombesin, administered by intravenous infusion (5 ng · kg^-1 · min^-1) for 60 min, significantly delayed gastric emptying of solids in man and strongly potentiated the gastrin response to food. However, no correlation was found between the difference in the integrated gastrin response (to meal and to meal plus bombesin) and the degree of delay in emptying. The effect of the peptide is most likely connected with the strong contraction of the gastroduodenal junction pinpointed in previous investigations.

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