Release of [3H]norepinephrine from nerves in rat colonic mucosa: effects of norepinephrine and prostaglandin E2.

Release of [3H]norepinephrine ([3H]NE) from noradrenergic nerves innervating rat colonic mucosa was studied by superfusion of a muscle-stripped preparation of rat colon. After a period of incubation with [3H]NE, the tissue was superfused with different releasing agents. Depolarization of the tissue with a medium containing 50 mM K+ evoked the release of [3H]NE. Veratridine (5 X 10(-5) M) also stimulated the efflux of [3H]NE; this was blocked by tetrodotoxin (2 X 10(-7) M). Tyramine, which releases NE by a nondepolarizing mechanism, also evoked [3H]NE release from the colonic mucosal preparation, and this release was not decreased in the absence of calcium. Exogenous NE (10(-7) M) inhibited the high K+-evoked release by 50% in the presence of desmethylimipramine, a NE uptake inhibitor. In addition, prostaglandin E2 (1 X 10(-7) M) significantly reduced the K+-evoked release to less than 50% of control. Pretreatment with 6-hydroxydopamine, which selectively destroys NE neurons, reduced the K+-evoked release of [3H]NE to 40% of control. This study suggests that colonic mucosa of the rat contains noradrenergic nerves that function in a manner characteristic of the noradrenergic nerves in other tissues.