Potentiation Between Gastrin and Histamine in Stimulation of Gastric Secretion.

Abstract

During studies on Heidenhain pouches in dogs we noted that the responses to certain combinations of gastrin extract plus histamine were greater than would be anticipated on the basis of summation of stimulatory effects ( 1 ) .The study reported here was performed to determine whether the combination of gastrin plus histamine resulted in true potentiation of stimulation of secretion of acid.Methods. Four dogs with Heidenhain pouches were fasted overnight before each study and studies were performed no oftener than twice a week. Gastrin and histamine were given by continuous intravenous injection using a calibrated peristaltic pump that delivered 20 ml/hr. An infusion of 01.15 M NaCl at this rate was maintained throughout the study and the concentration of gastrin and histamine in the infusion fluid was varied to give the desired dosage rates. Gastrin was prepared from mucosa of the pyloric gland area of the stomach of hogs by a method previously described ( 1 ) . Doses of gastrin are expressed as the wet weight of mucosa from which the extract was derived. Doses of histamine are expressed as weight of the dihydrochloride salt. Collections of gastric juice were made every 15 minutes. The volume was measured and the acidity determined by titration with 0.2 N NaOH with phenol red indicator. Output of acid is expressed as niEq/hr for the last 60 minutes of each 75-minute period.As pointed out previously, the simple criterion that response to a combination of agents given simultaneously is greater than the sum

Acid secretion by isolated canine gastric mucosa.

“…Maximal responses to histamine and gastrin are equal in dogs with vagally innervated main stomach (gastric fistulas) when the drugs are given by continuous intravenous infusion (Passaro & Grossman, 1964). However, the maximal acid response of the vagally denervated Heidenhain pouch to gastrin is only 45 % of that to histamine (Gillespie & Grossman, 1963).…”

“…No inhibitory effects of histamine on the isolated dog gastric mucosa were observed at histamine concentrations up to 8 x 10-4 M. In vivo, supramaximal doses of histamine infusion have been demonstrated to produce a comparable or a slightly lower secretary rate than maximal acid secretion in the gastric fistula preparation (Marks, Komarov & Shay, 1960) and in the Heidenhain pouch (Gillespie & Grossman, 1963). Intravenous infusions of gastrin (Gillespie & Grossman, 1963) and acetylcholine into the arteries of the gastric fundus of the dog (Pevsner & Grossman, 1955) have been demonstrated to elicit stimulation of acid secretion at low dosage rates and suppression of acid secretion at high rates.…”

“…Intravenous infusions of gastrin (Gillespie & Grossman, 1963) and acetylcholine into the arteries of the gastric fundus of the dog (Pevsner & Grossman, 1955) have been demonstrated to elicit stimulation of acid secretion at low dosage rates and suppression of acid secretion at high rates. The present studies demonstrate that there are optimal concentrations for gastrin and acetylcholine to stimulate acid secretion.…”

“…Grossman and his colleagues (Anderson & Grossman, 1965;Gillespie & Grossman, 1964;Johnson & Grossman, 1969;Passaro, Gillespie & Grossman, 1963) have reported that in the innervated or denervated dog stomach potentiation of gastric acid secretion occurs with urecholine and gastrin, urecholine and histamine and gastrin and histamine. However, Hirschowitz, Sachs & Hutchison (1973) did not observe potentiation or synergism between histamine and pentagastrin in the gastric fistula dog preparation.…”

Pharmacological Activities of T-Amyloxy-Carbonyl Tryptophanyl-Methionyl-Asparatyl-Phenylalanine Amide

“…Grossman et al reported that the maximal response to combination of two agents was greater than the maximal responses to either agent alone in dogs with Heidenhain pouch for the com bination of bethanechol plus gastrin (19) and gastrin plus histamine (20). Although, as Makhlouf et al (11) pointed out, the few attempts to demonstrate such potentiation in human subjects have not succeeded.…”