The isolated stomach preparation of the mouse: a physiological unit for pharmacological analysis

Abstract

Although oxyntic cell secretion can be studied at many organisation levels between isolated cell suspensions and non‐invasive techniques in animals, the isolated, lumen‐perfused, stomach preparation of the mouse represents a hierarchical level which eliminates extrinsic regulatory influences but retains all the cellular architecture known to be necessary for physiological responses and so can be defined as the physiological unit of acid secretion. The feeding pattern before and the distending pressure during an experiment have been identified as the main determinants of basal secretion: the combination of an intragastric pressure of 12 cmH2O and the fasted state generated a stable basal secretion over 2 h providing a satisfactory basis for bioassays. Basal acid secretion was lowered by treatment with omeprazole and sodium thiocyanate but not with tetrodotoxin, N‐methylatropine or tiotidine, suggesting that basal secretion does not involve nervous stimulation or the local release of histamine under these experimental conditions. The improved assay permitted the full characterization of cumulative agonist concentration‐effect curves in single stomach preparations to histamine, 5‐methylfurmethide, pentagastrin and isobutylmethylxanthine. Interestingly, pentagastrin produced sustained stimulation of gastric acid secretion under conditions when there was no pharmacological evidence that histamine secretion was taking place. This finding is discussed in relation to the role of histamine in the control of gastric acid secretion.

Evidence that the apparent complexity of receptor antagonism by angiotensin II analogues is due to a reversible and syntopic action

“…These parameters, expressed as mean ± s.e., were used for subsequent analysis and display of data (see Black & Shankley, 1985 for details).…”

Pharmacological analysis of the inhibition by pirenzepine and atropine of vagal‐stimulated acid secretion in the isolated stomach of the mouse

“…Gastric acid secretion was measured in the isolated, lumen-perfused, stomach preparation of the mouse as described previously (Black & Shankley, 1985a Electrical field stimulation of the vagus was achieved, essentially, by the methods used by Angus & Black (1982). A pair of platinum, ring, electrodes (ring diameter 2 mm, wire diameter 0.5 mm) were placed either side ofthe stomach to stimulate the region of the fundic glands.…”

“…This conclusion was based on the ratios of concentrations of atropine and pirenzepine needed to inhibit by 50% (IC50) a single response to both bethanechol and vagalstimulated acid secretion. In this study, we extend their analysis by examining the effects of pirenzepine and atropine on fully-defined frequency-effect curves on an improved, isolated stomach assay preparation of the mouse (Black & Shankley, 1985a). …”

The use of receptor desensitization to analyse CCKA and CCKB/gastrin receptors coupled to contraction in guinea‐pig stomach muscle

“…Concentration-effect curve data from individual preparations were fitted by means of an interactive least squares minimisation programme to a general logistic function to provide estimates of the midpoint location (log[Aj]), midpoint slope parameter (p) and upper asymptote (a) of the curves as described previously (Black & Shankley, 1985). These parameters, expressed as mean ± s.e.mean, were used for subsequent analysis (Student's t test or one-way analysis of variance, as appropriate) and display of the data.…”