INHIBITION OF SHAM FEEDING-STIMULATED ACID-SECRETION IN DOGS BY IMMUNONEUTRALIZATION OF GASTRIN

A monoclonal antibody to gastrin was used to study the role of circula ting gastrin in mediating acid secretion stimulated by sham feeding in dogs. On separate days, four conscious, fasted, adult mongrel dogs wi th esophageal and gastric fistulae were pretreated intravenously with either 7 mg of gastrin monoclonal antibody (MAb 28.2), 7 mg of keyhole limpet hemocyanin monoclonal antibody as control, or 12.5 mu g/kg atr opine sulfate. Thirty minutes later, acid secretion was stimulated fir st by sham feeding for 5 min, then, 60 min later, by an intravenous in fusion of a maximum stimulatory dose of histamine (40 mu g/kg) for 60 min, and after returning to basal, by intravenous infusion of a submax imal stimulatory dose of gastrin (200 pmol.kg(-1).h(-1)) for 60 min. A cid output from secretions collected every 15 min by gravity drainage was determined by titration to pH 7.0 with 0.2 N NaOH. Sham feeding-st imulated acid output (17.7 +/- 5.5 mmol/h) was significantly inhibited by administration of either MAb 28.2 (0 mmol/h) or atropine (1.7 +/- 1.1 mmol/h). Histamine-stimulated acid output (19.6 +/- 3.4 mmol/h) wa s not reduced by either pretreatment. Gastrin-stimulated acid output ( 3.9 +/- 0.6 mmol/h) was significantly reduced only by pretreatment wit h MAb 28.2 (0.1 +/- 0.1 mmol/h) and not by atropine (2.2 +/- 1.4 mmol/ h). A background intravenous infusion of pentagastrin (0.5 mu g.kg(-1) .h(-1)) restored sham feeding-stimulated acid output blocked by admini stration of MAb 28.2, although the intrinsic acid response to sham fee ding could not be seen with the background pentagastrin infusion. Furt hermore, the plasma gastrin response to sham feeding was not blocked b y atropine pretreatment. Because immunoneutralization of both gastrin and cholinergic blockade significantly inhibited acid output during sh am feeding, circulating gastrin and cholinergic pathways are involved in mediating the cephalic phase of gastric acid secretion in dogs.