Glial alpha 2-receptors probably inhibit the high-affinity uptake of noradrenaline into astrocytes in the rat brain in vivo.
The effect of alpha 2-receptor blockage on the extraneuronal turnover of noradrenaline (NA) has been studied in the intact rat brain. Tropolone and yohimbine, along with reserpine or desmethylimipramine, were given 30 min after intracerebroventricular injection of [7-3H]NA, i.e. after the tracer had been stored or inactivated. Tropolone given alone did not change the fractions of 3H-activity recovered as [3H]NA from hypothalamus, septum, striatum and pons-medulla, but in the presence of yohimbine improved the [3H]NA recovery in all areas except pons-medulla. The maximum effect was seen in the hypothalamus of reserpine-treated rats. Since the alpha 2-autoreceptors were blocked, the increased [3H]NA recovery does not reflect a down-regulated neuronal NA turnover. Instead it seems to show that a fraction greater than normal of neuronally released NA had been taken up into astrocytes and remained unmetabolized if catechol-O-methyltransferase was inactive. It is assumed that yohimbine enabled the protective tropolone effect by blocking astrocytic alpha 2-receptors that otherwise, either by itself or by antagonizing beta-receptor-induced hyperpolarization or cAMP formation, had impaired parameters that stimulate the high-affinity NA Uptake 1 of astrocytes (e.g. membrane potential, Na+,K(+)-ATPase) or control the gap junction permeability in the glial syncytium.
Köster
G
G
Institut für Klinische Biochemie, Universität, Bonn, Germany.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D005246:Feedback; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology; D014334:Tropolone / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D014334:Tropolone; D012110:Reserpine; D003891:Desipramine; D009638:Norepinephrine