EFFECT OF HUMAN GASTRIN-17 WITH AND WITHOUT ACID SUPPRESSION ON HUMANESOPHAGEAL MOTILITY

The putative role of gastrin for the regulation of esophageal motility is a matter of debate. Accordingly it was the aim of this study a) to examine if physiological postprandial plasma levels of human gastrin- 17 (hG-17) can affect esophageal motility, especially the pressure of the lower esophageal sphincter (LESP), and b) to assess the contributi on of augmented acid secretion during gastrin infusion. In a first ser ies of experiments postprandial plasma gastrin levels were determined in 8 healthy volunteers following the ingestion of a mixed meat. Gastr in rose from a baseline of 21 +/- 2 pg/ml to 67 +/- 8 pg/ml and return ed almost to basal levels within 120 minutes. In a second experimental series the effect of i.v. synthetic human gastrin-17 (hG-17) was stud ied in 17 volunteers. At a lower dose of 0.75 ng/kg/min hG-17 increase d plasma gastrin to 62 +/- 7 pg/ml while a higher dose of 1.5 ng/kg mi n elicited a supraphysiological increase to 119 +/- 11 pg/ml. Infusion of hG-17 caused a significant increase of the LESP from 19.0 to 25.8 mmHg (p < 0.05, low dose) and from 18.5 mmHg to 23.3 mmHg (p < 0.05, h igh dose) when compared to the effect of i.v. saline. To exclude effec ts of augmented acid secretion during hG-17 infusion the experiments w ere repeated after complete blockade of acid secretion with famotidine 40 mg i.v. After famotidine pretreatment hG-17 caused a similar incre ase of LESP from 20.1 to 25.9 mmHg (low dose) and from 19.9 to 24.1 mm Hg (high dose). Esophageal contraction amplitudes and propagation velo city were not significantly affected by gastrin infusion with or witho ut famotidine. In conclusion the present data demonstrate that a physi ologic increase of plasma gastrin levels increases LESP in humans. Thi s effect is independent of and unaffected by augmented acid secretion. Thus, gastrin has to be considered as a physiologically relevant modu lator of esophageal motility and its role in pathophysiological states such as reflux esophagitis should be examined in greater detail.