Radioimmunoassay of Histamine

Abstract

Waldum HL, Sandvik AK, Brenna E, Schulze Sögnen B. Radioimmunoassay of histamine. Scand J Gastroenterol 1991, 26(suppl 180), 32–39

Histamine is formed by decarboxylation of the amino acid histidine and is found both in plants and in animals, including man. In man it has important biologic functions. To assess the physiologic role of histamine, however, it is necessary to have a reliable and convenient method to determine its concentration in biologic fluids and tissue. Histamine has been determined by bioassay, chemically by different modification of a fluorometric method, by radioenzymatic methods, and, recently. by immunoassays. Immunoassay of histamine has, however, been difficult to establish, mainly as a result of problems with the production of an antibody with histamine specificity. This is due to the general occurrence of histamine in all animal species. By binding histamine to different ligands, several researchers have succeeded in producing antibodies against antigens in which histamine is integrated. Treating samples and histamine standard with the same coupling agent, reliable and specific radioimmunoassays of histamine have been established. We have for some years utilized a commercial radioimmunoassay of histamine and confirmed its convenience, specificity, and sensitivity. In some patients taking a histamine-2 blocker (cimetidine or ranitidine) we have detected an increase in plasma histamine which also tended to be increased after proximal gastric vagotomy and in patients with gastric ulcer compared with patients with duodenal ulcer. In rats treated with high doses of omeprazole for 90 days we found an increase in the enterochromaffin-like cell mass and in histamine concentration in the oxyntic mucosa which was reflected by an increase in plasma histamine. In the totally isolated vascularly perfused rat stomach we found that gastrin stimulation resulted in an increase in the histamine secretion parallel to the acid secretion. and histamine in the venous effluent increased immediately and con-centration-dependently. By comparing the effect of gastrin on histamine release and acid secretion with the effect of histamine on acid secretion, we have shown that the gastrin stimulation of acid secretion may be fully explained by the release of histamine. Finally, by comparing the histamine concentration in the venous effluent by means of two different radioimmunoassays (the Immunotech method, specific for histamine, and the Pharmacia method, with a 20–fold higher sensitivity for t-methyl histamine than for histamine itself), we could not find any indication that histamine is methylated in the stomach.

Key Words:

• Gastric acid
• gastrin
• histamine
• radioimmunoassay