Release of [3H]-amezinium from cortical noradrenergic axons: a model for the study of the alpha-autoreceptor hypothesis.
1 [(3)H]-amezinium is taken up selectively into noradrenergic axons and their transmitter-storing vesicles and is released from these axons by action potentials. We used it as a non-alpha-adrenergic marker in order to study the alpha-adrenergic autoinhibition of noradrenaline release.2 Rat occipitocortical slices were preincubated with [(3)H]-amezinium 0.03 muM and then superfused and stimulated electrically (3 Hz for 3 min). The stimulation-evoked overflow of tritium was measured in six groups of slices: from saline-pretreated rats; from saline-pretreated rats, the slices being exposed to exogenous noradrenaline before preincubation with [(3)H]-amezinium; from saline-treated rats, slices from which were exposed simultaneously to noradrenaline and cocaine before preincubation with [(3)H]-amezinium; from rats in which noradrenaline stores had been depleted by pretreatment with alpha-methyltyrosine (alpha-MT); from alpha-MT-treated rats, the slices being exposed to noradrenaline before preincubation with [(3)H]-amezinium; and from alpha-MT-treated rats, slices from which were exposed to noradrenaline plus cocaine before preincubation with [(3)H]-amezinium.3 The stimulation-evoked overflow of tritium, expressed as a percentage of the tritium content of the tissue, was 1.15% in slices from saline-pretreated rats, and was similar in slices from saline-pretreated rats after exposure to noradrenaline or noradrenaline plus cocaine. It was 2.56% in slices from alpha-MT-treated rats, 1.20% from alpha-MT-treated rats after exposure to noradrenaline, and 2.88% from alpha-MT-treated rats after exposure to noradrenaline plus cocaine.4 Yohimbine 0.1 and 1 muM increased the stimulation-evoked overflow of tritium in slices from all groups of saline-pretreated rats and in those slices from alpha-MT rats that had been in contact with exogenous noradrenaline. Yohimbine did not change the evoked overflow in slices from alpha-MT rats that had not been exposed to noradrenaline, or had been exposed to noradrenaline plus cocaine.5 Clonidine 0.01-1 muM decreased the stimulation-evoked overflow of tritium moderately in slices from saline-pretreated rats, markedly in slices from alpha-MT-treated rats, and moderately again when the latter slices had been exposed to noradrenaline.6 It is concluded that the action potential-evoked release of [(3)H]-amezinium as well as the modulation of this release by yohimbine and clonidine depend on the presence or absence of alpha-adrenergic autoinhibition caused by the co-secretion of noradrenaline. When there is co-secretion of noradrenaline, the evoked release of [(3)H]-amezinium is relatively small, yohimbine increases the release, and clonidine can cause only moderate inhibition. When there is no or very little co-secretion of noradrenaline, the evoked release of [(3)H]-amezinium is at least doubled, yohimbine causes no further increase and clonidine produces strong inhibition.
D000818:Animals; D001369:Axons / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D008954:Models, Biological; D009638:Norepinephrine / Q000502:physiology*; D011724:Pyridazines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013997:Time Factors; D019805:alpha-Methyltyrosine
D002395:Catecholamines; D008781:Methyltyrosines; D011724:Pyridazines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D019805:alpha-Methyltyrosine; C027784:amezinium; D009638:Norepinephrine