Lower oesophageal sphincter response to gastrin--pharmacological or physiological?

Abstract

SUMMARY The response of the lower oesophageal sphincter (LOS) to intragastric instillation of protein was assessed in 10 healthy volunteers. Sphincter pressures were measured by a rapid pullthrough technique and serum gastrin concentrations during each test were determined by radioimmunoassay. Despite stimulation of gastrin release by protein instillation, no significant change in LOS pressure was observed. However, intravenous pentagastrin (0 25 and 0.5 jig/kg) produced an immediate increase in sphincter pressure, which then returned to the basal level within four minutes. Thus, although pentagastrin is an effective pharmacological stimulant of the sphincter, endogenous gastrin appears not to be a physiological determinant of LOS pressure in man.The role of endogenous gastrin in control of the lower oesophageal sphincter (LOS) is still a subject of controversy. There is no doubt that exogenous gastrin increases sphincter pressure (Giles et al., 1969;Cohen and Lipshutz, 1971;Trindade et al., 1975;Kaye et al., 1976) but the evidence that endogenous gastrin is a physiological determinant of sphincter pressure is less convincing (Grossman, 1973;Roszkowski et al., 1973;Farrell et al., 1974;McCall et al., 1975; Dodds et al., 1975a, b;Dent and Hansky, 1976). Central to the controversy is the methodology of LOS pressure measurement. Most studies have used static pressure recording catheters or a station pull-through technique in which the recording catheter is withdrawn across the sphincter in 1 cm steps, pausing after each step to record LOS pressure during three or four respiratory cycles. Rapid pull-through techniques are now available which minimise error in pressure recording (Dodds etal., 1975a(Dodds etal., , b 1976) and a rapid pull-through method was used in the present study to measure the LOS pressure response to endogenous gastrin release provoked by intragastric instillation of protein. Methods TECHNIQUE OF LOS PRESSURE MEASUREMENT LOS pressure was measured by a rapid pull-through technique based on that described by WaldeckReceived for publication 9 August 1977 (1972) and modified by Osborne and his colleagues (1977). Recordings were made with a single lumen polyvinyl tube which was perfused at 6 ml/min as it was withdrawn across the LOS at 0'9 cm/s. This system was capable of recording a pressure rise rate of 70 mmHg/s when tested on the bench. By convention, LOS pressure is measured as the peak height of the profile relative to intragastric pressure. RESPONSE OF LOS TO PENTAGASTRINFour healthy male volunteers (aged 26-32 years), without a previous history of dyspepsia, were given graded doses of pentagastrin (Peptavlon, ICI) to determine the LOS pressure response. Doses of 0'0625, 0 125, 0-25, and 0 5 jig/kg were used, the pentagastrin being diluted in 10 ml/150 mm sodium chloride solution and injected intravenously over 60 seconds. The four doses were given in a random order which was not known to the subject. LOS pressure was measured every two minutes for 10 minutes before pentagastrin injectio...

Altered oesophageal motility following the administration of the 5‐HT1 agonist, sumatriptan

“…In contrast, the effect of sumatriptan 6 mg on lower oesophageal sphincter pressure was not maintained for nearly as long (≈ 1 h). A similar transient increase in lower oesophageal sphincter pressure has been noted in healthy subjects following, for example, pentagastrin 34 and gastrin 35 administration and could suggest that this short‐lived response is a characteristic of the lower oesophageal sphincter. Indeed, in vitro studies have suggested that the smooth muscle of the oesophageal body and lower oesophageal sphincter do possess different sensitivities to various compounds 36 .…”

Plasma concentration of neurotensin‐like immunoreactivity (NTLI) and lower esophageal sphincter (LES) pressure in man following infusion of (GIn4)‐neurotensin

“…Therefore, neurotensin, or a neurotensin metabolite, might be responsible for the decrease in the LES pressure after a fatty meal. Several hormones released after food intake, such as gastrin, secretin, cholecystokinin, and glucagon, have been shown to influence the LES pressure (Nebel & Castell 1972, Giles et al 1969, Castell & Harris 1970, Cohen & Lipshutz 1971, Resin et al 1973, Jaffer et al 1974, but it has not been established whether these hormones are of any physiological importance in the regulation of the LES pressure (Grossman 1973, Cohen & Lipshutz 1974, Sturdevant 1974, Henderson et al 1978.…”

Active and Inactive Gastroesophageal Reflux Diseases Related to Helicobacter pylori Therapy

“…However, when endogenous gastrin release was stimulated by calcium gluconate, ZES patients showed increased LES pressure [63]. Besides ZES, previous studies revealed that a high dose of pentagastrin, a gastrin analog, increased LES pressure, but a low dose of gastrin did not [65][66][67]. Whereas gastrin-I (gastrin-17), one of the physiological gastrins, gives a conflicting result, Heil et al and Jennewein et al reported that a high dose of gastrin-17 induced an increased LES pressure, as did pentagastrin [68,69].…”