Gizzerosine Raises the Intracellular Cyclic Adenosine-3′,5′-Monophosphate Level in Isolated Chicken Proventriculus

Gizzerosine, which was originally found in fish meal, is a compound that causes gizzard erosion and ulceration in chicks. The action of gizzerosine on the isolated cells of chicken proventriculus was studied in the present investigations. Gizzerosine increased intracellular cyclic adenosine-3',5'-monophosphate (cAMP) levels, reaching a plateau within 30 min. Similar maxima of cAMP level were observed in the presence of histamine or gizzerosine. However, the potency of gizzerosine was approximately 1,000-fold higher than that of histamine. The action of gizzerosine was depressed by cimetidine, a histamine H2-receptor antagonist, but not by pyrilamine, a histamine H1-receptor antagonist, indicating that gizzerosine is a very strong histamine H2-receptor agonist. The mucosal cells isolated from the proventriculus by the present procedure had both histamine H1 and H2-receptors. Gizzerosine showed a higher affinity to the cell surface histamine receptor than histamine. These results partly explain the potent activity of gizzerosine in inducing gastric acid secretion and causing gizzard erosion and ulceration in chickens.