The physiological role of histamine in the exocrine pancreas.

In addition to the autonomic nervous system and gut hormones, the mast cell mediator histamine has also been associated with exocrine pancreatic secretion. This review is concerned with the distribution and the physiological role of histamine in the control of pancreatic juice secretion. Histamine is distributed widely around blood vessels and acinar tissues in the pancreas and it is released in pancreatic juice during secretagogue stimulation. Histamine has a marked secretagogue effect in the exocrine pancreas of several animal species but in many cases the secretory effect is gender-related. The paracrine hormone exerts its secretory response via activation of H1 and H2 receptors on pancreatic acinar cells to mobilize potassium ions (K+) and cellular calcium (Ca2+) and through elevation of endogenous adenosine 3',5' cyclic monophosphate (cyclic AMP) levels, respectively. A physiological role for H3 receptors has also been associated with exocrine pancreatic secretion. H3 receptors are located presynaptically on parasympathetic nerve terminals to control the release of acetylcholine via restriction of Ca2+ access into nerve terminal through the N-type Ca2+ channel. Taken together, the results presented in this review strongly support histamine as a potential modulator of exocrine pancreatic function.