The effect of endomorphins on the release of 3H-norepinephrine from rat nucleus tractus solitarii slices

Abstract

We used two, 3-min field stimulation cycles 30 min apart (S1, S2) in 3H-norepinephrine-loaded, superfused rat nucleus tractus solitarii-dorsal motor vagal nucleus (NTS-DVN) slices. The stimulation-induced release was expressed as the area above the baseline. Drugs were introduced 12 min before S2 and drug actions were characterized in terms of alterations of S2/S1 ratios. The S2/S1 ratio was 1.047 (0.946–1.159, n=4, geometric mean and 95% confidence interval) in controls and 0.336 (0.230–0.490, n=3), 0.726 (0.590–0.892, n=4), 0.613 (0.594–0.683, n=4) and 0.665 (0.500–0.886, n=4) in the presence of 10 −6 M clonidine, d-Ala 2,MePhe 4,Gly 5-ol-enkephalin (DAMGO), endomorphin-1 (Tyr–Pro–Trp–Phe–NH 2, EM-1) and -2 (Tyr–Pro–Phe–Phe–NH 2, EM-2) [the latter two in the presence of 10 −4 M diprotin A, an inhibitor of dipeptidyl-aminopeptidase IV (DAP-IV) enzyme]. The effect of DAMGO at 10 −5 M was significantly higher than at 10 −6 M, whereas the effect of endomorphins did not differ at the two concentration levels. Diprotin A potentiated only very modestly the action of endomorphins. These data (a) confirm the presence of functional μ-opioid receptors in the vagal complex, (b) render it likely that the enzymic degradation of endomorphins is not a highly effective process in brain slices and (c) may suggest that the apparent ceiling in the effect of endomorphins might be related to their partial agonist property.