REGULATION OF ION-TRANSPORT BY HISTAMINE IN HUMAN COLON

Histamine, added to the basolateral side of voltage clamped human colon in vitro, induced a rapid onset, transient inward short circuit current which was concentration dependent over the range 0.01-3 mM. This response was largely due to electrogenic chloride secretion since it was virtually abolished by bumetanide or by chloride replacement in the bathing solutions. Responses were unaffected by amiloride or acetazolamide. Neither the histamine H-2 receptor agonist dimaprit (1 mM) nor the histamine H-3 receptor agonist S-(+)-alpha-methyl histamine (1 mM) altered short circuit current. Responses to histamine were significantly reduced by the histamine H-1 receptor antagonist mepyramine (1-10 mu M) but not altered by the histamine H-2 receptor antagonist cimetidine (100 mu M) or by the histamine H-3 receptor antagonist thioperamide (1 mu M). Short circuit current responses to histamine were not altered by tetrodotoxin (1 mu M). Piroxicam (10 mu M) and nordihydroguaiaretic acid (100 mu M) were without effect when used individually but significantly reduced responses to histamine when used simultaneously. These results indicate that histamine stimulates chloride secretion across human colonic epithelium by a mechanism which is mediated exclusively via histamine H-1 receptors. This action does not involve intrinsic nerves but appears to be dependent upon eicosanoid synthesis.