Effect of histamine on pancreatic exocrine secretion in the dog

The effect of histamine on the secretion of pancreatic juice was investigated in preparations of isolated, blood-perfused dog pancreas. Histamine (3-30 microgram) injected intra-arterially caused dose-dependent increases in the secretion of pancreatic juice after a delay of a few minutes. 4-Methylhistamine (10-100 microgram), a selective histamine H2-receptor agonist, caused changes of the pancreatic secretion similar to those of histamine. Metiamide (100 microgram), a selective H2-receptor antagonist, blocked the increases of the pancreatic secretion in responses to both histamine or 4-methylhistamine. In contrast, diphenhydramine even at large doses (1 mg), a selective H1-receptor antagonist, did not effect histamine, or 4-methylhistamine-induced secretion. Histamine increased both bicarbonate and protein concentration in the juice. This action was different from that of secretion or pancreozymin. These results suggest that histamine increases pancreatic secretion acting directly on pancreatic cells through H2-receptors.