Functional properties of noradrenergic nervous system in rat colonic mucosa: uptake of [3H]norepinephrine.

The accumulation of exogenous [3H]norepinephrine ([3H]NE) by rat colonic mucosa was studied. Uptake was linear for 10 min and reached a maximum after 90 min. The process was concentration dependent and saturable, having a Km of 1.67 X 10(-6) M and Vmax of 0.57 nmol.g-1.min-1. The inhibitor of specific norepinephrine uptake, desmethylimipramine (DMI), inhibited uptake in a concentration-dependent manner; the maximum inhibition was 81% at 10 microM. Normetanephrine also inhibited uptake at 100 microM. Reserpine, at concentrations ranging from 10(-7) to 10(-5) M, prevented the accumulation of [3H]NE, with maximum inhibition being 47% of control. Accumulation by mucosa obtained from rats sympathectomized with 6-hydroxydopamine was only 33% of control; DMI did not further reduce this uptake. Colonic epithelial cells were isolated and were found to also accumulate [3H]NE, but this accumulation was not affected by DMI. It is concluded that rat colonic mucosa contains noradrenergic neurons capable of accumulating exogenously administered norepinephrine by a specific and high-affinity process. The presence of a functional noradrenergic neural network in close association with the epithelium suggests that this system may play a physiological role in modulating colonic mucosal function.