Suppression of rat stomach histidine decarboxylase activity by histamine: H2-receptor-mediated feed-back.
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 H(2)-receptor blockade, but not after H(1)-receptor blockade, histamine was less effective in suppressing the enzyme activity. Furthermore, H(2)-receptor blockade augmented the pentagastrin-induced enzyme activation.5. The results suggest that histamine (via H(2)-receptors) reduces the sensitivity of the histamine-storing cells to gastrin and that H(2)-receptor blockade induces the opposite effects.6. We propose that the histamine-storing cells in the rat stomach are endowed with H(2)-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.
D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D003864:Depression, Chemical; D005743:Gastrectomy; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology; D005755:Gastrins / Q000097:blood; D006632:Histamine / Q000494:pharmacology*; D006640:Histidine Decarboxylase / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D010418:Pentagastrin / Q000494:pharmacology; D011706:Pyloric Antrum / Q000502:physiology; D051381:Rats; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D013270:Stomach / Q000187:drug effects / Q000201:enzymology*; D014628:Vagotomy
D005755:Gastrins; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D006632:Histamine; D002262:Carboxy-Lyases; D006640:Histidine Decarboxylase; D010418:Pentagastrin