Letter | Published:

Do presynaptic auto-receptors control dopamine release?

Nature volume 274, pages 706708 (17 August 1978) | Download Citation

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Abstract

MANY studies have attempted the elucidation of the homeostatic mechanisms controlling the amount of neurotransmitter released in the synapse. There is convincing evidence that the release of noradrenaline (NA), from both peripheral and central presynaptic nerve endings, can be modulated by a negative feedback mechanism, whereby the neurotransmitter present in excess in the synapse depresses its further release by activating specific presynaptic α-receptors, α-Agonist drugs interact similarly to NA with these receptors and inhibit the depolarisation-induced release of the amine, whereas α-antagonists counteract this inhibitory effect1–10. The appealing concept of a feedback control of neurotransmitter release, although unequivocally demonstrated only for NA, has been generalised to other transmitters. This generalisation seems rather premature. In particular, the existence of presynaptic autoreceptors controlling dopamine (DA) release is often accepted2,7,11,12; however, recent observations13,14 argue against this interpretation and, as pointed out by Langer15, the presence of a direct control of DA release by presynaptic receptors remains an open question. In our studies on DA release described here, our experimental approach differs in two main aspects from those used previously13,14. First, we have monitored the release of 3H-DA synthesised from 3H-tyrosine, in addition to that of exogenous 3H-DA previously taken up by the nerve terminals. Newly synthesised DA is preferentially released by depolarising stimuli16 and may therefore be preferentially influenced by a feedback mechanism. Second, we have used superfused synaptosomes. In our conditions17,18, the DA released is immediately removed from the nerve endings and any autoinhibition of release is minimised. Therefore, presynaptic receptors are completely available to the agonists (which should decrease the depolarisation-induced release) or the antagonists added to the superfusion fluid. Our results show that the DA agonists have no effect on the stimulus-coupled release of DA, either taken up or newly synthesised, from striatal synaptosomes, and therefore militate against a direct control of DA release through presynaptic autoreceptors similar to that demonstrated for NA.

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Affiliations

  1. Istituto di Farmacologia, Università Cattolica, Rome

    • M. RAITERI
    • , A. M. CERVONI
    •  & R. DEL CARMINE
  2. Laboratorio di Biologia Cellulare, CNR, Rome, Italy

    • G. LEVI

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https://doi.org/10.1038/274706a0

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