The metabolism of [³H]noradrenaline released by electrical stimulation from the isolated nictitating membrane of the cat and from the vas deferens of the rat

Drug‐induced changes in the release of [3H]‐noradrenaline from field stimulated rat iris

“…GD131, a 8-haloalkylamine similar to phenoxybenzamine (Nickerson & Gump, 1949), which inhibits neuronal as well as extraneuronal uptake without blocking the a-adrenoceptors (Furchgott & Kirpekar, 1963;Kalsner & Nickerson, 1969) (Iversen & Langer, 1969;Kalsner & Nickerson, 1970;Levin & Furchgott, 1970;Langer, 1970) since no effect is obtained with the COMT-inhibitor 4-tropolone-acetamide (Ross & Haljasmaa, 1964). Previous work has shown that inhibition of MAO by nialamide does not increase tritium overflow from field stimulated rat iris (Farnebo, 1971).…”

“…Phenoxybenzamine inhibits extraneuronal uptake of NA (Iversen, 1965;Eisenfeld et al, 1967) and this has been suggested one explanation for the increased NA overflow using this drug (Iversen & Langer, 1969;Langer, 1970 which inhibits extraneuronal uptake (Iversen, 1965;Eisenfeld et al, 1967).…”

“…After incubation with low concentrations of [3H]-NA (10-6M or lower) more than 90% of the tritium content is intraneuronally located [3H]-NA (Jonsson et al, 1969). Field stimulation increases tritium overflow from superfused tissue previously incubated with [3H]-NA (Baldessarini & Kopin, 1967;Farnebo & Hamberger, 1970a, b;Haggendal, Johansson, Jonasson & Ljung, 1970;Langer, 1970;Su & Bevan, 1970). The stimulation-induced tritium overflow from irides of untreated rats consists mainly of unchanged [3H]-NA (Farnebo, 1971).…”

“…Estimation of the total overflow of radioactivity might be more relevant than estimation of unchanged [3H]-NA alone, since the major metabolism is likely to occur after the release from the nerve terminal (cf. Langer, 1970).…”

Sixth Gaddum Memorial Lecture National Institute for Medical Research, Mill Hill, January 1977

“…The possible significance of the inhibition by phenoxybenzamine of extraneuronal uptake became apparent after it was reported in studies on transmitter release carried out with [3H]-noradrenaline, that a significant fraction of the 3H-transmitter released by nerve stimulation was collected as ]3Hi-noradrenaline metabolites (Langer, 1970; Figure 2 Schematic representation of the negative feed-back mechanism for noradrenaline released by nerve stimulation, mediated by presynaptic aadrenoceptors. Noradrenaline (NA) released by nerve stimulation once it reaches a threshold concentration in the synaptic cleft activates presynaptic aadrenoceptors leading to inhibition of transmitter release.…”