Correlation between serum gastrin concentration and rat stomach histidine decarboxylase activity.
After prolonged fasting the activity of histidine decarboxylase in the oxyntic mucosa of the rat stomach is low. Feeding or injection of gastrin or insulin rapidly raises the enzyme activity. It was earlier suggested that all enzyme-activating agents act through release of gastrin. This view has found experimental support in studies which show that in antrectomized rats the enzyme is activated by gastrin but not by gastrin-releasing stimuli like feeding or vagal excitation (insulin hypoglycemia). In the present investigation rats were subjected to a variety of treatments and serum gastrin concentrations and gastric histidine decarboxylase activities were measured. The main findings were as follows.1. Feeding raised the serum gastrin level and the enzyme activity in unoperated rats. In fasted antrectomized rats the serum gastrin concentration was low; in freely fed antrectomized rats it was at the same level as in fasted unoperated rats. In antrectomized rats the enzyme activity was low and not raised by feeding.2. Acid in the antrum inhibits the release of gastrin whereas an alkaline pH may facilitate such release. All treatments that blocked acid secretion, thereby raising the antral pH, also raised the serum gastrin concentration and concomitantly the histidine decarboxylase activity. Thus, vagotomy increased the serum gastrin level and the histidine decarboxylase activity in fasted rats. Treatment of fasted unoperated rats with atropine or hexamethonium had similar effects. Antral exclusion, which prevents HCl from reaching the pyloric glands, resulted in marked increase in the serum gastrin concentration and in the enzyme activity of fasted rats.3. Injection of insulin resulted in a rather slow, progressive increase in the serum gastrin concentration. The peak was reached after about 4 hr. The enzyme activity was also raised markedly and the peak response occurred about 1 hr later.4. An increase in the histidine decarboxylase activity was invariably preceded or accompanied by a raised serum gastrin level. With fasted or fed unoperated, vagotomized, antrectomized or antrally excluded rats, the correlation coefficient for the relation between enzyme activity and serum gastrin concentration was 0.69 (P < 0.05).5. Porta-caval-shunted fasted rats responded to feeding or injection of insulin with marked activation of gastric histidine decarboxylase. The response after feeding was at least 5 times higher in shunted than in nonshunted rats but serum gastrin was only slightly higher. Following antrectomy of porta-caval-shunted rats feeding no longer raised the enzyme activity. Thus, the enzyme-activating agent was of antral origin. In the shunted rats injection of pentagastrin induced an enzyme activation about 5 times that seen in intact rats. This response was not significantly reduced by antrectomy. In conclusion, we have observed a correlation between serum gastrin concentration and histidine decarboxylase activity. We have failed to obtain evidence for the existence of any physiological intermediate other than gastrin in the activation of histidine decarboxylase induced by feeding, vagal stimulation or inhibition of acid secretion.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002262:Carboxy-Lyases / Q000032:analysis*; D005215:Fasting; D005247:Feeding Behavior; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology*; D005755:Gastrins / Q000097:blood*; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006639:Histidine; D007328:Insulin / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D011167:Portacaval Shunt, Surgical; D011706:Pyloric Antrum / Q000601:surgery; D011863:Radioimmunoassay; D051381:Rats; D014628:Vagotomy
D002250:Carbon Radioisotopes; D005755:Gastrins; D006584:Hexamethonium Compounds; D007328:Insulin; D007457:Iodine Radioisotopes; D006639:Histidine; D001285:Atropine; D002262:Carboxy-Lyases; D010418:Pentagastrin