Influence of 5-hydroxytryptamine uptake on the apparent 5-hydroxytryptamine antagonist potency of metoclopramide in the rat isolated superior cervical ganglion.

Metoclopramide, 1 X 10(-6) -1 X 10(-4) M, was found to behave as a reversible, competitive antagonist of 5-hydroxytryptamine (5-HT)-induced depolarization of the rat isolated vagus nerve (VN) and superior cervical ganglion (SCG). The pKB values were 6.60 (+/- 0.04) and 5.74 (+/- 0.07), respectively. The possibility that this apparent difference in potency was due to saturable 5-HT uptake was investigated. The SCG, but not the VN, accumulated tritium-labelled 5-HT via a saturable, sodium- and temperature-dependent mechanism. Ganglionic 5-HT uptake was blocked by desmethylimipramine (IC50 1.4 X 10(-6)M), chlorimipramine (8.7 X 10(-9) M), zimelidine (1.5 X 10(-7) M), paroxetine (4.3 X 10(-8) M) and citalopram (6.2 X 10(-8) M). The 5-HT uptake inhibitor paroxetine, 1 X 10(-6) M, did not modify the apparent 5-HT antagonist potency of metoclopramide on the VN, but raised the pKB obtained against 5-HT on the SCG from 5.74 (+/- 0.07) to 6.25 (+/- 0.03). It is suggested that the observed difference in the potency of metoclopramide as a 5-HT antagonist on the rat VN and SCG was due to saturable 5-HT uptake in the latter preparation. The results do not support a difference in the 5-HT receptors mediating depolarization on the VN and SCG.