Most neurotransmitter systems have some sort of autoreceptor function. Autoreceptors are generally G-protein coupled receptors rather than ionotropic receptors. They affect the cell through activation of second messenger transduction. The dopamine D2 receptor, norepinephrine alpha 2a and alpha 2c adrenoreceptors, acetylcholine M2 and M4 muscarinic receptors, and histamine H3 receptors are examples of common autoreceptors expressed in the nervous system. Index pages. Got a question?
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MANY studies have attempted the elucidation of the homeostatic mechanisms controlling the amount of neurotransmitter released in the synapse. 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 accepted 2,7,11,12 ; however, recent observations 13,14 argue against this interpretation and, as pointed out by Langer 15 , 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 previously 13, First, we have monitored the release of 3 H-DA synthesised from 3 H-tyrosine, in addition to that of exogenous 3 H-DA previously taken up by the nerve terminals. Newly synthesised DA is preferentially released by depolarising stimuli 16 and may therefore be preferentially influenced by a feedback mechanism.
Second, we have used superfused synaptosomes. In our conditions 17,18 , 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.
Farnebo, L. Acta physiol. Enero, M. Starke, K. Naunyn-Schmiedebergs Archs Pharmak. Langer, S. Dismukes, R. Taube, H. Dismukes, K. Westfall, T. Plotsky, P. Science , — Raiteri, M.
Alterations of the number or responsiveness of autoreceptors may play a role in the pathogenesis of diseases which are related to a disturbed function of the respective neurones in the peripheral or central nervous system. As an example, the potential importance of autoinhibitory alpha 2-adrenoceptors and autofacilitatory beta 2-adrenoceptors activated by the cotransmitter adrenaline; both receptors located on sympathetic nerve fibres and of autoinhibitory presynaptic 5-HT1B receptors located on central serotoninergic nerves in the development of essential hypertension is discussed.
Autoreceptors may play a role in the therapeutic effect of currently available drugs, and it is probable that new classes of drugs which act predominantly via this site will be developed.
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