Human lower esophageal sphincter responses to synthetic human gastrins 34 (G-34) and 17 (G-17)

Abstract Gastrin is a potent stimulant of human lower esophageal sphincter pressure (LESP), but previous studies have indicated that G-17 is not likely to be the major physiologic regulator of LESP in humans. The effects of big gastrin (G-34) on human LESP have not been reported previously. This study was conducted to determine the pharmacologic and possible physiologic effects of G-34 on LESP in normal human subjects. Equimolar rapid injections of synthetic human G-17 and G-34 in doses ranging from 6.25 to 100 pmol/kg resulted in similar dose-related increases in LESP that commenced within 2 min after injection of either peptide. After rapid intravenous injection, the threshold change in serum gastrin for stimulation of LESP was more than 100 fmol/ml for both peptides. The LESP returned to baseline within 15 min after G-17, but remained elevated for more than 45 min after G-34. The magnitude of LES responses to equal increments of G-34 was less at 30 min than at 10 min, indicating a loss of sensitivity to this peptide over time. Continuous intravenous infusion of G-34, 100 pmol · kg −1 · hr −1 , and of G-17, 200 pmol · kg −1 · hr −1 , significantly increased LESP above control values and produced similar peak responses. During G-17 and G-34 infusions, the threshold change in serum gastrin estimated to produce any increase in LESP was 30–50 fmol/ml, half maximal responses were obtained at approximately 140 fmol/ ml, and maximal responses were achieved with increases of 210–290 fmol/ml above baseline values. Intragastric instillation of 10% peptone resulted in a mean peak increase in total gastrin of 58 fmol/ml, well below the change in serum gastrin necessary for half maximal LESP responses. Neither the peptone meal nor the control saline meal produced a significant increase in LESP in these subjects. It is concluded that: (a) circulating G-17 and G-34 have similar potency for stimulation of human LESP, (b) the total change in serum G-17 and G-34 after a peptone meal approached the threshold stimulation of LESP for these forms of gastrin but was accompanied by no significant increase in LESP, and (c) G-17 and G-34 are not likely to be physiologic regulators of the human LES.