Is Histamine Able to Maintain an Augmented Pepsin Response Comparable to That of Pilocarpine?

Bucher, Gladys R.; Ivy, A. C.; Gray, John S.

doi:10.1152/ajplegacy.1941.132.3.698

Cited by 20 publications

(6 citation statements)

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“…This finding would support the suggestion that a washout of preformed pepsin does not totally explain the pepsin response following stimulation with these drugs (Bucher, Ivy, and Gray, 1941;Hirschowitz, London, and Pollard, 1957;Gillespie and Bowen, 1962;Makhlouf, McManus, and Card, 1967). The initial peak response could be compatible with such a washout effect, but the continuing steady state of pepsin secretion would suggest that both drugs are true stimulants of the pepsin-forming cells.…”

Section: Commentsupporting

confidence: 64%

The effects on human gastric secretion of prolonged continuous intravenous infusions of maximal and supramaximal doses of histamine acid phosphate and pentagastrin

Aubrey¹

1970

Gut

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SUMMARY The effects of continuous intravenous infusions of 'maximal' and 'supramaximal' doses of histamine acid phosphate and pentagastrin were assessed in a normal human volunteer. The secretory patterns in respect of the two drugs were indistinguishable over two and a quarter hours. During the steady states of acid secretion, outputs of pepsin and of electrolytes were also constant. The output of acid during the first hour of the steady state is a valid measurement of the maximal secretory capacity. The constant output of pepsin during the steady state of acid secretion suggests that both drugs are true stimulants of pepsin secretion.After a single subcutaneous injection of histamine acid phosphate, as in the augmented histamine test (Kay, 1953), the output of acid rises towards a peak, which is transient and occurs at a variable time during the first hour after the administration of the drug (Baron, 1963). The transient nature of this response leaves considerable room for error in the estimation of the maximal output of acid, particularly in states characterized by low secretion (Lawrie, Smith, and Forrest, 1964). When a maximal dose of histamine or pentagastrin is administered by continuous intravenous infusion the output of acid rises to reach a plateau or steady state (Lawrie et al, 1964;Konturek and Lankosz, 1967). The calculation of the maximal secretory capacity is not then dependent on the observation and interpretation of a peak response, and hence there is less room for error in calculating the maximal output of acid than in the augmented histamine test.The study reported now was undertaken to determine respectively (1) whether the maximal gastric secretory outputs of acid, pepsin, and electrolytes were sustained when histamine acid phosphate and pentagastrin were administered, by continuous intravenous infusion, for prolonged periods, and (2) whether the outputs of these constituents in the first hour of steadystate conditions were a valid assessment of this state.Received for publication 21 October 1969. Methods TESTS OF SECRETIONTwelve tests of gastric secretion were performed on one subject, a normal healthy male volunteer aged 52 years. He received in random sequence, on three occasions each, 40 and 80 ,tg/kg/hr of histamine acid phosphate and 6.0 and 12-0 ,ug/kg/hr of pentagastrin. Each test was preceded by a fast of at least 12 hours, and at least three days intervened between tests.In the tests using histamine, a prior injection of mepyramine maleate was given to counteract side effects; 50 mg was given before a dose of 40 gg/kg/hr and 100 mg before a dose of 80 ,tg/kg/hr.The stimulants were diluted in 0.9 % saline, and their concentrations in solution were dependent on the dose required according to body weight. The rates of infusion were controlled by a Palmer constant infusion pump and varied from 5 37 to 1 174 ml per hour.

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Section: Commentsupporting

confidence: 64%

The effects on human gastric secretion of prolonged continuous intravenous infusions of maximal and supramaximal doses of histamine acid phosphate and pentagastrin

Aubrey¹

1970

Gut

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“…Alternatively, it may be that the pepsin-secreting cells are also, to a slight degree, under histamine control (Bucher, Ivy, and Gray, 1941), so the reduction in pepsin secretion may also be due to a specific anti-histamine effect.…”

Section: Discussionmentioning

confidence: 99%

The inhibitory action of a locally applied antihistamine on canine gastric secretion induced by peripheral parasympathetic stimulation

Kay

Forrest

1956

British Journal of Surgery

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I N a previous paper we have shown that in Heidenhain pouch dogs the secretion of acid in response to histamine can be prevented by irrigating the pouch with an antihistamine (promethazine). We considered this inhibition to be due to specific antagonism between histamine and the antihistamine : but Robertson and Grossman (1952) in similar studies have attributed it to damage of the gastric mucosa caused by the direct irritant action of the antihistamine.In the present paper we present similar studies in which the pouch secretion has been provoked not by histamine but by carbaminoyl-,!?-methyl choline chloride, which stimulates pepsin as well as acid production. We shall show that the anti-histamine selectively inhibits the acid production. We believe that this supports the view that its action is not a non-specific effect but a pharmacological antagonism. METHOD OF STUDYFour dogs with separated pouches of the stomach (Heidenhain type) were used. Animals were fasted for a period of 16 hours before each test. Secretion of juice, rich in acid and pepsin, was stimulated by carbaminoyl-@-methyl choline chloride (Mecothane-Savory & Moore), given by subcutaneous injection in a dose of 0.25 mg. quarter-hourly for a period of 29 hours. During this period juice was collected at 15 minute intervals, the volume measured in ml., and the concentration of free hydrochloric acid determined by titration with decinormal sodium hydroxide, using Topfer's solution (p-dimethyl aminoazobenzine) as indicator. From these values, the output of hydrochloric acid for each 15 minute period was calculated in milliequivalents. During each test in each dog specimens of hourly or half hourly juice were obtained by pooling aliquots of each 15 minute collection. The concentration of pepsin in these pooled samples was estimated by the method of Hunt (1948) using dried human serum as substrate. The peptic activity has been expressed in milligrammes of tyrosine-like substances liberated from the substrate per ml, of juice, and the product of the hourly or half-hourly volume of juice, and its peptic activity represents the output of pepsin in mg. of tyrosine equivalents per hour or half hour.The effect of locally applied antihistamine on the secretory response to mecothane was determined by irrigating the pouch with a solution of promethazine hydrochloride (6 mg. per ml. 0.9 per cent saline) for a half hour period before commencing the mecothane injections. The method of irrigation was as previously described (Kay and Forrest, 1956). Three tests were performed on each of the 4 dogs. In three control experiments on each animal, the pouch was irrigated with 0.9 per cent saline alone. MECOTHANE 0 . 2 5 mqm ocr 15 minutes. OUTPUT OF PEPSIN I : : ] mq. TYROSINE Eqs. 0 VOLUME OF JUICE 2,0 0 ml. 0 -4 0 0 I 2 HOURS FIG. 11z.-The secretory response of a separated gastric pouch in a dog to repeated subcutaneous injections of carbaminoyl-p-methyl choline chloride.In the control studies the acid and pepsin responses to repeated subcutaneous injections of mecotha...

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“…Babkin (1944) and others have argued that since the histamine-stimulated secretion of pepsin may be low and since repeated injections may cause a further fall in concentration, the histamine secretion represents only a washing out of pepsin from the gastric pits. Goodman (1938), however, found a rise in pepsin on repeated injection, while have criticized the deductions made from the "double histamine" method (see, e.g., Gilman and Cowgill, 1931), and Bucher, Ivy, and Gray (1941) suggest that histamine, like such substances as pilocarpine, should be regarded as a stimulant for pepsin. More recently, Bjorkman, Norden, and Uvnas (1943), using anaesthetized cats with the pylorus ligated, failed to find a rise in pepsin activity and indeed found a decline after histamine injection, whereas vagal stimulation caused a marked rise.…”

Section: Discusionsmentioning

confidence: 99%

“…Alley (1935) has even postulated an inhibitory effect ofhistamine on pepsin secretion. More recently, however, Bucher, Ivy, and Gray (1941) have claimed that pepsin is increased in the stomach of the dog after histamine injection ; this work has been strongly criticized by Babkin (1944). In man, a number of clinical studies (e.g., Polland, 1932) suggested a stimulation of pepsin output after histamine, and Toby (1937a) found that the peptic content of human gastric juice was as high as that produced by stimulation of the vagus inthedog.…”

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confidence: 99%

The Action of Histamine on Hydrochloric Acid and Pepsin Secretion in Man

Ashford

Heller

Smart

1949

British Journal of Pharmacology and Chemotherapy

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Is Histamine Able to Maintain an Augmented Pepsin Response Comparable to That of Pilocarpine?

Cited by 20 publications

References 0 publications

The effects on human gastric secretion of prolonged continuous intravenous infusions of maximal and supramaximal doses of histamine acid phosphate and pentagastrin

The effects on human gastric secretion of prolonged continuous intravenous infusions of maximal and supramaximal doses of histamine acid phosphate and pentagastrin

The inhibitory action of a locally applied antihistamine on canine gastric secretion induced by peripheral parasympathetic stimulation

The Action of Histamine on Hydrochloric Acid and Pepsin Secretion in Man

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