Functional characterization of central α-adrenoceptors by yohimbine diastereomers

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Abstract

Rat occipital cortex slices were preincubated with [3H]noradrenaline and then superfused with medium containing 30 μM cocaine. They were stimulated electrically at 3 Hz. Unlabelled noradrenaline (0.1 μM), α-methylnoradrenaline (0.01–0.1 μM), xylazine (0.1–10 μM) and guanabenz (0.01 μM) decreased, whereas yohimbine (0.01–1 μM), rauwolscine (0.01–1 μM), corynanthine (10 μM), tolazoline (0.1–10 μM) and azapetine (0.1–1 μM) increased the stimulation-evoked overflow of tritium without a change in basal outflow. Pseudoyohimbine and prazosin at up to 0.1 μM did not change the evoked overflow, and at higher concentrations enhanced the basal outflow of tritium. In vivo, yohimbine 10 mg/kg and rauwolschine 10 mg/kg markedly, and corynanthine 10 mg/kg slightly accelerated the α-methyltyrosine-induced disappearance of noradrenaline from rat whole brain. Yohimbine and rauwolscine but not corynanthine also accelerated the α-methyltyrosine-induced depletion of dopamine. The results add four compounds to the list of drugs with α-adrenoceptor affinity which inhibit (agonists) or facilitate (antagonists) action-potential-evoked release of noradrenaline in rat brain cortex. The presynaptic receptors are of the α2-type. The receptors which control the activity of noradrenaline and dopamine neurons in vivo also appear to be α2.

References (32)

  • T. Tanaka et al.

    High selectivity of rauwolscine for presynaptic α-adrenoceptors

    European J. Pharmacol.

    (1978)
  • N.E. Andén et al.

    R 28935 and prazosin: effects on central and peripheral alpha-adrenoreceptor activity and blood pressure

    Naunyn-Schmiedeb. Arch. Pharmacol.

    (1978)
  • N.E. Andén et al.

    Different alpha-adrenoreceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents

    Naunyn-Schmiedeb. Arch. Pharmacol.

    (1976)
  • B.B. Brodie et al.

    Application of steady state kinetics to the estimation of synthesis rate and turnover time of tissue catecholamines

    J. Pharmacol. Exp. Ther.

    (1966)
  • C. Cambridge et al.

    The pharmacology of antihypertensive drugs with special reference to vasodilators, α-adrenergic blocking agents and prazosin

    Med. J. Aust. Special

    (1977)
  • L. Cubeddu et al.

    Release of norepinephrine and dopamine-β-hydroxylase by nerve stimulation. V. Enhanced release associated with a granular effect of a benzoquinolizine derivative with reserpine-like properties

    J. Pharmacol. Exp. Ther.

    (1975)
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