HISTAMINE SENSITIVITY OF MESENTERIC AFFERENT NERVES IN THE RAT JEJUNUM

The concept of functional interaction between mast cells and intestina l afferents is gaining support. We have therefore characterized the ac tion of histamine on jejunal afferent discharge in the anesthetized ra t. Whole nerve mesenteric afferent discharge was recorded in conjuncti on with intestinal pressure in response to a range of histamine agonis ts and antagonists. Histamine at 2, 4, and 8 mu mol/kg (iv) evoked a d ose-dependent biphasic increase in afferent discharge together with a biphasic rise in intestinal pressure. However, these two events were m ediated independently, since nifedipine (1 mg/kg) substantially reduce d the intestinal pressure increase but not the afferent discharge. The se responses were completely inhibited by pyrilamine (5 mg/kg) but una ffected by ranitidine (5 mg/kg) or thioperamide (2 mg/kg). Neither the selective H-2 receptor agonist dimaprit nor the selective H-3 recepto r agonist R-alpha-methylhistamine caused any modulation of efferent di scharge. We conclude that histamine stimulates an H-1 receptor-mediate d increase in mesenteric afferent discharge that is independent of int estinal motor events. This suggests that histamine potentially acts as a mediator in mast cell-to-afferent nerve communication in the small intestine.