Maximal acid secretory response to histamine and its relation to parietal cell mass in the dog

Marks, I. N.; Komarov, S. A.; Shay, Harry

doi:10.1152/ajplegacy.1960.199.3.579

Cited by 83 publications

(24 citation statements)

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“…The present study thus emphasizes the importance of considering the tone of both parts of the autonomic nervous system when studying gastric secretion even when induced by peripherally acting stimu lants. The remark of Marks et al [5] that the pepsin output is a better parameter of the tone in the autonomic nervous system than volume or acid output, is confirmed by our data after a single shot as well as by Hirschowitz [3] during continuous infusion.…”

Section: Discussionsupporting

confidence: 88%

Pentagastrin-Induced Gastric Secretion in Dogs

Ga¹

1972

Digestion

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Pentagastrin (0.2–6.4 μg/kg s.c.) given to conscious dogs supplied with a gastric fistula, caused a log dose-dependent gastric secretion of volume, H⁺, Na⁺, K⁺, Ca⁺⁺, Mg⁺⁺ and Cl^-. The pepsin output was at a similar level as after histamine, but much lower than after insulin-induced vagal stimulation. Atropine methyl nitrate (5 μg/kg i.v.) diminished the secretory response to pentagastrin; dihydroergotamine (40 μg/kg i.v.) augmented the pentagastrin-induced secretion. The significance of pepsin as parameter of the relative tone in the parasympathetic as well as in the sympathetic nervous system is emphasized.

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Section: Discussionsupporting

confidence: 88%

Pentagastrin-Induced Gastric Secretion in Dogs

Ga¹

1972

Digestion

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“…Marks, Komarov, and Shay (1960) (Morton and Stravraky, 1949) and it is possible that at critical levels of Urecholine dosage the addition of gastrin or histamine causes reversal of effects on pepsin but not on acid secretion.…”

Section: Methodsmentioning

confidence: 99%

Potentiation between Urecholine and gastrin extract and between Urecholine and histamine in the stimulations of Heidenhain pouches

Gillespie¹,

Grossman²

1964

Gut

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EDITORIAL SYNOPSIS These studies clearly establish the existence of true potentiation between Urecholine and gastrin and between Urecholine and histamine in stimulating secretion both of acid and of pepsin.It is frequently said that cholinergic activity, induced either by drugs or by vagal activity, 'potentiates' the acid secretory responses to gastrin or to histamine. The assumption that these combinations of stimuli act in a 'potentiated' rather than an 'additive' fashion is based upon the large augmentations that occur. So far as we have been able to determine, no previous study has provided data that can be analyzed in the manner required to determine whether the combined actions represent addition or potentiation (Gaddum, 1959). Now that methods are available for the preparation of reliably potent gastrin extracts (Gregory and Tracy, 1960) the problem can be studied both with histamine and with gastrin. To provide quantitative data suitable for answering the question about potentiation, we have studied the secretion of acid and pepsin by Heidenhain pouch dogs in response to a range of dose rates of Urecholine (urethane of ,B-methylcholine chloride, a stable choline ester that mimics the muscarinic actions of acetylcholine), gastrin extract, and histamine, given separately and in combination. METHODSObservations were made on five Heidenhain pouch dogs.On each day Urecholine (bethanechol chloride, Merck, Sharp, and Dohme) was given by continuous intravenous injection at a constant rate, the rates on different days varying from 0 25 to 4 mg. per hour. After two hours of Urecholine alone, gastrin extract or histamine dihydrochloride was given by a second continuous intravenous infusion while continuing the injection of Urecholine. The dose rate of gastrin extract or of histamine was doubled every 75 minutes. Secretory rates became relatively steady within 15 minutes ofstarting or increasing the dose of gastrin or of histamine. For this reason the one-hour output from 15 to 75 minutes after each alteration in dose rate was taken as a measure of the response to the combination of drugs. With all but the lowest doses of Urecholine, side-effects occurred, namely, increased salivation, micturition, and defaecation. Because of the severity of these side-effects no test was done with a dose of Urecholiiie greater than 4 mg. per hour. Control runs of Urecholine alone, gastrin extract alone, and histamine alone, over the same dose ranges used in the combined studies, were also done on separate days.Gastrin extracts were prepared from the mucosa of the pyloric gland area of hog stomach by a modification of the method of Gregory and Tracy (1960), as previously described (Gillespie and Grossman, 1963). A single pooled batch of gastrin extract was used for all of the studies reported here. Doses of gastrin are expressed in terms of the wet weight of mucosa represented by the extract.

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“…In experimental animals such as dogs, on the other hand, the acid secre tion continues to increase up to an intravenous histamine dose of 96-144 ¡xg/ kg/h [18], and 125 ¡xg/kg/h [11]. H ir sc h o w it z [12] has suggested that the observed inhibition [6,18] of acid secretion with very high doses may be an artifact of the experimental technique related to the decline in acid produc tion with time.…”

Section: Introductionmentioning

confidence: 99%

Dose-Response Relationship of Graded Doses of Intravenous Histamine Infusion on Gastric Acid Secretion in Man

Bajaj¹,

Goyal²,

Chuttani³

1974

Digestion

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Dose-response curves for the effect of continuous intravenous infusion of histamine on the gastric acid secretion was obtained in nine healthy volunteers of Indian origin. Each subject was studied with 5 doses (20, 40, 60, 80, and 100 μg/kg/h) of histamine acid phosphate administered for 3 h, on separate days, in random fashion. The plateau of secretion occurred in the 2nd h of infusion. The analysis of variance revealed that acid output significantly increased with increasing dose of histamine; the increase in acid output was significant at all dose levels except between 80 and 100 μg/kg/h. The analysis of data using dose of histamine independent of body weight gave a poorer fit to the regression line than that obtained with histamine dose on the basis of body weight, suggesting that dose of histamine should be administered on the basis of body weight. The estimate of calculated V_max and the dose of histamine producing a response 50% of V_max or (K_m) by the three different transformations of the Michaelis-Menten equation gave somewhat different values for both these constants. All these were slightly different from direct estimation of V_max and K_m with analysis of curvilinear regression. The linear transformation using the plot of C_s/v versus C_s gave the best results. The double reciprocal plot underestimated both the constants. The value of Km in Indian subjects was almost six times the value in Western subjects, indicating the relative insensitivity of the parietal cells to histamine in our subjects.

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Maximal acid secretory response to histamine and its relation to parietal cell mass in the dog

Cited by 83 publications

References 0 publications

Pentagastrin-Induced Gastric Secretion in Dogs

Pentagastrin-Induced Gastric Secretion in Dogs

Potentiation between Urecholine and gastrin extract and between Urecholine and histamine in the stimulations of Heidenhain pouches

Dose-Response Relationship of Graded Doses of Intravenous Histamine Infusion on Gastric Acid Secretion in Man

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