Histamine sensitivity of mesenteric afferent nerves in the rat jejunum

The concept of functional interaction between mast cells and intestinal afferents is gaining support. We have therefore characterized the action of histamine on jejunal afferent discharge in the anesthetized rat. Whole nerve mesenteric afferent discharge was recorded in conjunction with intestinal pressure in response to a range of histamine agonists and antagonists. Histamine at 2, 4, and 8 micromol/kg (iv) evoked a dose-dependent biphasic increase in afferent discharge together with a biphasic rise in intestinal pressure. However, these two events were mediated independently, since nifedipine (1 mg/kg) substantially reduced the intestinal pressure increase but not the afferent discharge. These responses were completely inhibited by pyrilamine (5 mg/kg) but unaffected by ranitidine (5 mg/kg) or thioperamide (2 mg/kg). Neither the selective H2 receptor agonist dimaprit nor the selective H3 receptor agonist R-alpha-methylhistamine caused any modulation of afferent discharge. We conclude that histamine stimulates an H1 receptor-mediated increase in mesenteric afferent discharge that is independent of intestinal motor events. This suggests that histamine potentially acts as a mediator in mast cell-to-afferent nerve communication in the small intestine.