ALPHA-ADRENOCEPTOR ANTAGONISTS AND THE RELEASE OF NORADRENALINE IN RABBIT CEREBRAL-CORTEX SLICES - SUPPORT FOR THE ALPHA-AUTORECEPTOR HYPOTHESIS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 84  (1) , 147-155
Abstract
Slices of rabbit cerebral cortex were preincubated with [3H]-noradrenaline [norepinephrine], and then were superfused and stimulated electrically, twice for 2 min each (S1, S2), at various frequencies (0.2-3 Hz). The stimulation-evoked overflow of 3H (S1) increased with increasing frequency, and was higher when cocaine (10 .mu.M) was present. In the absence of cocaine, tetraethylammonium (TEA; 100 and 300 .mu.M), added before S2, increased the stimulation-evoked overflow of 3H to about the same extent, irrespective of the frequency. In contrast, rauwolscine (0.1 and 1 .mu.M) and idazoxan (0.1-10 .mu.M) increased the evoked overflow much more, the higher the frequency of stimulation. Phentolamine (0.1 and 1 .mu.M) reduced the overflow elicited at 0.3 and 1 Hz, and (1 .mu.M) caused an increase only at 3 Hz. In slices superfused throughout with cocaine 10 .mu.M, rauwolscine (1 .mu.M) and idazoxan (1 and 10 .mu.M) again increased the evoked overflow of tritium more, the higher the frequency of stimulation. For a given freqency, rauwolscine and idazoxan enhanced the evoked overflow to a greater extent in the presence, than in the absence, of cocaine. Idazoxan (1 and 10 .mu.M) and rauwolscine (1 .mu.M) counteracted the inhibition that phentolamine (0.1 .mu.M) produced at low frequency. The increases caused by rauwolscine (1 .mu.M) and TEA (300 .mu.M) were approximately additive, but those caused by rauwolscine (1 .mu.M) and idazoxan (10 .mu.M) were not. The effects of rauwolscine idazoxan and phentolamine depend on the experimental conditions (frequency, cocaine), in a manner compatible with the operation of a presynaptic .alpha.2-adrenoceptor-mediated autoinhibition of noradrenaline release. When given at sufficient concentrations, these antagonists enhance the release of noradrenaline so that the biophase concentration of the transmitter is higher and the autoinhibition is stronger. In the case of the partial .alpha.2-adrenoceptor agonist phentolamine, a low perineuronal noradrenaline concentration even reverses facilitation to inhibition. This pattern differs markedly from the pattern of effects of TEA, which increases the release of noradrenaline by a mechanism other than .alpha.-adrenoceptor blockade.