ACTIVATION OF HISTIDINE DECARBOXYLASE BY H₂‐RECEPTOR BLOCKADE: MECHANISM OF ACTION

Abstract

1 Treatment with histamine H 2-receptor antagonists, which inhibit basal acid secretion, was found to activate rat stomach histidine decarboxylase. At the same time the serum gastrin concentration was greatly increased. 2 In antrectomized rats neither the enzyme activity nor the serum gastrin concentration was affected by the treatment. 3 In analogy with pr,,vious observations on other inhibitors of acid secretion we suggest that the H 2-receptor antagonists stimulate gastrin release through their effect on acid secretion and that the raised serum gastrin level is responsible for the enzyme activation.

Effects of cimetidine upon gastric secretion and mucosal blood flow in the rat stressed by restraint

“…But gastrin was not significantly increased (Table 2) in these short-term experiments, similar to data from short-term studies in humans [3]. Therefore, a marked acid reduction in the absence of hypergastrinemia disagrees with the operation of a simple feedblack loop linking juice pH and antral G-cell activity, but suggests more complex events among these two factors if CT is simultaneously present [14].…”

Evidence for H2‐receptor‐mediated feed‐back regulation of histamine release from endocrine cells in the rat stomach.

“…If the serum gastrin concentration is raised sufficiently, gastric histamine is released and gastric histidine decarboxylase is activated. These effects of H2-receptor antagonists on the histamine cells are indirect (HAkanson et al 1975). The results of the present and a previous study (HAkanson et al 1977) have disclosed an additional, direct effect of H2-receptor antagonists on the histamine cells in the gastric mucosa.…”

The effects ofl-histidine, and of specific histamine receptor agonists, on the expression of morphine tolerance and physical dependence in mice

“…We are dealing here with a complex situation in the central nervous system. It is known that these two methylated histamines can cause accumulation of histamine in the brain [21,22], and this accumulated histamine, together with endogenous histamine, will act on both H I-and H2-receptors. However, unpublished data from this laboratory suggest that the elevation of brain histamine arising in this way is unlikely to be great enough to account for the whole of the effects observed with the methylated amines.…”