Mechanisms of extraneuronal serotonin uptake in the rat aorta

The mechanisms of extraneuronal serotonin (5-HT) uptake in the rat aorta were studied. Aortic strips were pretreated with 0.1 mM pargyline and incubated with 0.1 to 9.1 microM 5-HT (5-HT, 0.02-1.60 microgram/ml including [3H]-5-HT, 0.02 microgram/ml) for 1, 2, 3 and 5 min at 37 degrees C. Accumulation of [3H]sorbitol was used to correct for extracellular distribution of this amine. The initial rate of 5-HT uptake was related linearly to the substrate concentration within the tested range. Cocaine, imipramine, desipramine (10 microM each), Na+-free solution and cooling (0 degrees C) inhibited markedly both the 1- and 5-min uptake of 5-HT. Removal of the endothelium did not affect the 5-HT uptake for 1 min but reduced slightly that for 5 min. Corticosterone (10 microM), norepinephrine (10 microM) and 6-hydroxydopamine pretreatment did not affect the uptake of 5-HT. Autoradiography demonstrated that uptake of 5-HT for 5 min in the rat aorta occurs primarily at the smooth muscle cells near the lumen. These results suggest that the rat aorta has a large capacity of cocaine-sensitive extraneuronal uptake of 5-HT. This uptake appears to occur primarily in the muscle layers adjacent to the lumen, suggesting that the muscle cells of the luminal side function differently from those from the adventitial side. The mechanism of the extraneuronal uptake of 5-HT appears to be different from that of norepinephrine and the extraneuronal uptake of 5-HT occurs initially in a nonsaturable mode and later through a Na-dependent, carrier-mediated transport.