Further evidence for an intestinal phase hormone that stimulates gastric acid secretion.
The studies described in this report were directed at isolating the hormone responsible for the intestinal phase of gastric acid secretion. One hundred and ten extracts of hog intestinal mucosa, each representing the yield from about 3,000 hogs, were prepared by a method for isolating small peptides that involved heating, absorption on diethylaminoethylcellulose (DEAE), and acid precipitation. All extracts stimulated gastric acid secretion in acute gastric fistula rats, and 56 were highly active according to stringent criteria that required a greater than 50 percent increase in acid output above basal in at least 60 percent of rats. Increasing doses of extract stimulated increasing acid production according to a regular dose-response relationship. Twelve highly active extracts were tolerated without side effects when infused into dogs with Heidenhain pouches and produced a mean 22 fold increase in acid output above basal. The gastrin content of 73 extracts, measured by radioimmunoassay in two independent laboratories, averaged 5,80 ng. per rat dose of extract, which is approximately 1/500 of the minimal stimulating dose of hog gastrin. No extract contained sufficient gastrin to produce an acid secretory response. Administration of the extract together with a maximal stimulating dose of pentagastrin in rats significantly augmented the maximal acid secretory response. Finally, comparison of the acid secretory response to portal and systemic intravenous infusion of the extract in acute gastric fistula rats demonstrated significant inactivation by passage through the liver, in contrast to the results of similar studies of hog gastrin. It is concluded that the extract had all of the known physiologic properties of the intestinal phase hormone and very likely contained the intestinal phase hormone.
D000818:Animals; D001681:Biological Assay; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005745:Gastric Acidity Determination; D005750:Gastric Juice / Q000378:metabolism* / Q000502:physiology; D005755:Gastrins / Q000032:analysis; D006728:Hormones / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000032:analysis; D010418:Pentagastrin / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D012636:Secretory Rate / Q000187:drug effects; D013268:Stimulation, Chemical; D013552:Swine; D014020:Tissue Extracts / Q000494:pharmacology*
D005755:Gastrins; D006728:Hormones; D014020:Tissue Extracts; D010418:Pentagastrin