Displacement of norepinephrine by alpha-methylnorepinephrine in the nucleus tractus solitarius of the rat.

Rat brain slices from the dorsomedial medulla containing the nucleus tractus solitarius were loaded with [3H]norepinephrine ([3H]NE) for superfusion. Electrical stimulation (3 Hz, 25 mA, 1 min) resulted in fractional release ratios S2/S1 of 0.97 +/- 0.02 in normal Krebs-Henseleit (KH) and 0.93 +/- 0.06 in the presence of 30 microM cocaine. With cocaine in the KH medium, L-alpha-methylnorepinephrine (alpha-MeNE) significantly reduced the [3H]NE release S2/S1 without affecting the basal release ratios. Without cocaine in the KH medium both 0.1 and 1.0 microM alpha-MeNE increased the basal release B2/B1 that was not affected by yohimbine. Prazosin had no effect on the S2/S1 ratio but did attenuate the basal release effects of alpha-MeNE. In low Ca2+ studies where the S2 stimulus was abolished, 1.0 microM alpha-MeNE induced a sharply elevated increase in the B2/B1 ratio. It appears that alpha-MeNE in the presence of the uptake inhibitors reduces presynaptic neurotransmitter release through alpha 2-adrenoceptors, whereas when uptake of the monoamines was not blocked alpha-MeNE was considerably more efficacious as a displacing agent of neurotransmitter.