Abstract
1. Gastrin activates rat stomach histidine decarboxylase. Exogenous histamine suppressed the basal enzyme activity in unoperated, in nephrectomized, in vagally denervated and in antrectomized rats, and counteracted the pentagastrin-induced enzyme activation in unoperated rats.
2. Kinetic analysis of enzyme-catalysed histidine decarboxylation in extracts from untreated vagotomized and from histamine-treated vagotomized rats showed that the histamine-induced suppression of histidine decarboxylase activity probably reflects a reduced enzyme concentration. Moreover, the enzyme half-life in vagotomized rats after treatment with histamine was shorter than the half-life observed after inhibition of enzyme synthesis. These observations suggest that administration of histamine not only inhibits enzyme synthesis but also causes an accelerated rate of elimination of histidine decarboxylase.
3. Intravenous infusion of histamine caused marked displacement of the pentagastrin dose—response curve, in a manner suggesting a reduced sensitivity to pentagastrin.
4. After H2-receptor blockade, but not after H1-receptor blockade, histamine was less effective in suppressing the enzyme activity. Furthermore, H2-receptor blockade augmented the pentagastrin-induced enzyme activation.
5. The results suggest that histamine (via H2-receptors) reduces the sensitivity of the histamine-storing cells to gastrin and that H2-receptor blockade induces the opposite effects.
6. We propose that the histamine-storing cells in the rat stomach are endowed with H2-receptors and that exogenous histamine is capable of acting directly on the histamine cells. This may reflect a physiological control mechanism whereby mobilized endogenous histamine modifies its own synthesis and release.
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Selected References
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- El Munshid H. A., Liedberg G., Rehfeld J. F., Sundler F., Larsson L. I., Håkanson R. Effect of bilateral nephrectomy on serum gastrin concentration, gastric histamine content, histidine decarboxylase activity, and acid secretion in the rat. Scand J Gastroenterol. 1976;11(1):87–91. [PubMed] [Google Scholar]
- Henningsson S., Lundell L., Rosengren E. Comparative study of two isotopic methods determining histamine formation in vitro. Biochem Pharmacol. 1974 Oct 1;23(19):2671–2678. doi: 10.1016/0006-2952(74)90037-9. [DOI] [PubMed] [Google Scholar]
- Häkanson R., Hedenbro J., Liedberg G., Rehfeld J. F., Stadil F. Activation of histidine decarboxylase by H2-receptor blockade: mechanism of action. Br J Pharmacol. 1975 Jan;53(1):127–130. doi: 10.1111/j.1476-5381.1975.tb07339.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Håkanson R., Kroesen J. H., Liedberg G., Oscarson J., Rehfeld J. F., Stadil F. Correlation between serum gastrin concentration and rat stomach histidine decarboxylase activity. J Physiol. 1974 Dec;243(2):483–498. doi: 10.1113/jphysiol.1974.sp010763. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Håkanson R., Liedberg C. The activation of rat stomach histidine decarboxylase is independent of the histamine level. Experientia. 1971;27(11):1279–1280. doi: 10.1007/BF02136685. [DOI] [PubMed] [Google Scholar]
- Håkanson R., Liedberg G. Effect of pentagastrin and feeding on gastric histidine decarboxylase activity in the antrectomized rat. Eur J Pharmacol. 1972 Apr;18(1):31–36. doi: 10.1016/0014-2999(72)90128-8. [DOI] [PubMed] [Google Scholar]
- Håkanson R., Liedberg G. Effects of brocresine (NSD-1055) and cycloheximide on amino acid decarboxylase activities in gastric mucosa of normal and vagally denervated rats. Br J Pharmacol. 1972 Dec;46(4):688–695. doi: 10.1111/j.1476-5381.1972.tb06893.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Håkanson R., Liedberg G. Evidence against histamine as final chemostimulator of gastric acid secretion. Am J Physiol. 1971 Aug;221(2):641–643. doi: 10.1152/ajplegacy.1971.221.2.641. [DOI] [PubMed] [Google Scholar]
- Håkanson R., Liedberg G. Mechanism of activation of rat stomach histidine decarboxylase after vagal denervation. Eur J Pharmacol. 1971 Sep;16(1):78–89. doi: 10.1016/0014-2999(71)90059-8. [DOI] [PubMed] [Google Scholar]
- Håkanson R., Liedberg G., Rehfeld J. F. Is the basal activity of rat stomach histidine decarboxylase affected by antrectomy? Experientia. 1975 Dec 15;31(12):1398–1399. doi: 10.1007/BF01923208. [DOI] [PubMed] [Google Scholar]
- Håkanson R., Liedberg G. The role of endogenous gastrin in the activation of gastric histidine decarboxylase in the rat. Effect of antrectomy and vagal denervation. Eur J Pharmacol. 1970 Sep 1;12(1):94–103. doi: 10.1016/0014-2999(70)90033-6. [DOI] [PubMed] [Google Scholar]
- Johansson I., Lundell L., Rosengren E., Svensson S. E. Gastric secretion and its facilitation as related to gastric mucosal histamine. J Physiol. 1972 Oct;226(2):431–452. doi: 10.1113/jphysiol.1972.sp009992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KAHLSON G., ROSENGREN E., SVAHN D., THUNBERG R. MOBILIZATION AND FORMATION OF HISTAMINE IN THE GASTRIC MUCOSA AS RELATED TO ACID SECRETION. J Physiol. 1964 Nov;174:400–416. doi: 10.1113/jphysiol.1964.sp007494. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kahlson G., Rosengren E., Thunberg R. Accelerated mobilization and formation of histamine in the gastric mucosa evoked by vagal excitation. J Physiol. 1967 Jun;190(3):455–463. doi: 10.1113/jphysiol.1967.sp008221. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kim K. S., Ridley P. T., Tuegel C. Effect of insulin on gastric acid secretion, histamine formation, and on the incidence of gastric lesions. Life Sci. 1968 Apr 1;7(7):403–409. doi: 10.1016/0024-3205(68)90011-8. [DOI] [PubMed] [Google Scholar]
- Levine R. J., Watts D. E. A sensitive and specific assay for histidine decarboxylase activity. Biochem Pharmacol. 1966 Jul;15(7):841–849. doi: 10.1016/0006-2952(66)90161-4. [DOI] [PubMed] [Google Scholar]
- Lundell L. Histamine metabolism of the gastric mucosa following antrectomy. J Physiol. 1974 Sep;241(2):437–451. doi: 10.1113/jphysiol.1974.sp010665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lundell L., Rosengren E., Svensson S. E. Alterations in histamine metabolism of rat gastric mucosa following vagotomy. J Physiol. 1974 Oct;242(1):209–218. doi: 10.1113/jphysiol.1974.sp010702. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rehefeld J. F. Three components of gastrin in human serum. Gel filtration studies on the molecular size of immunoreactive serum gastrin. Biochim Biophys Acta. 1972 Dec 28;285(2):364–372. [PubMed] [Google Scholar]
- Rehfeld J. F. Disturbed islet-cell function related to endogenous gastrin release. Studies on insulin secretion and glucose tolerance in pernicious anemia. J Clin Invest. 1976 Jul;58(1):41–49. doi: 10.1172/JCI108457. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rehfeld J. F., Stadil F., Rubin B. Production and evaluation of antibodies for the radioimmunoassay of gastrin. Scand J Clin Lab Invest. 1972 Oct;30(2):221–232. doi: 10.3109/00365517209081114. [DOI] [PubMed] [Google Scholar]
- SNYDER S. H., AXELROD J. TISSUE METABOLISM OF HISTAMINE -C14 IN VIVO. Fed Proc. 1965 May-Jun;24:774–776. [PubMed] [Google Scholar]
- Schwartz J. C., Ronnberg A. L., Cohen Y., Valette G. Histamine formation in rat stomach: study of regulation mechanisms. Eur J Pharmacol. 1969 Feb;5(3):272–278. doi: 10.1016/0014-2999(69)90148-4. [DOI] [PubMed] [Google Scholar]
- Stadil F., Rehfeld J. F. Preparation of 125 I-labelled synthetic human gastrin I for radioimmunoanalysis. Scand J Clin Lab Invest. 1972 Dec;30(4):361–368. doi: 10.3109/00365517209080271. [DOI] [PubMed] [Google Scholar]
- Weidle E., Sewing K. F. The effect of submaximal doses of pentagastrin on gastric acid secretion, histamine and histidine decarboxylase in rats. J Pharm Pharmacol. 1973 Mar;25(3):234–238. doi: 10.1111/j.2042-7158.1973.tb10630.x. [DOI] [PubMed] [Google Scholar]