Inhibitory heteroreceptor , presynaptic

Scanziani M, Capogna M, Gahwiler BH, Thompson SM (1992) Presynaptic inhibition of miniature excitatory synaptic currents by baclofen and adenosine in the hippocampus. Neuron 9 919-27 Schlicker E, Gothert M (1998) Interactions between the presynaptic alpha2-autoreceptor and presynaptic inhibitory heteroreceptors on noradrenergic neurones. Brain Res Bull 47 129-32. Schmitz D, Mellor J, Nicoll RA (2001) Presynaptic kainate receptor mediation of frequency facilitation at hippocampal mossy fiber synapses. Science 291 1972-6 Schneggenburger R, Neher E (2005) Presynaptic calcium and control of vesicle fusion. Curr Opin Neurobiol 15 266-74... 

Both mianserin and mirtazapine are antidepressant drugs which possess central 0C2 adrenoceptor blocking properties (pA2 7.3). However, mirtazapine is much more potent at histamine Hi receptors (pA2 9.1) and at 5-HT2 and 5-HT3 receptors (pA2 8.2). Blocking of Hi receptors explains the main side effects of mirtazapine, which produces marked sedation and weight gain. Blockade of presynaptic inhibitory 0C2 autoreceptors increases the release of NA, while blockade of presynaptic 0C2 inhibitory heteroreceptors on serotonin nerve terminals (Table 2) is likely to increase the release of serotonin. 

We do not know whether the interactions between the presynaptic receptors occur on the level of the receptors or on a site beyond the receptor level, e.g. on the level of G proteins, ion channels or other second messengers. Such receptor interactions may explain drug interactions in vivo. They are also of importance for planning in vitro experiments. H3 receptor-mediated effects in superfused slice preparations are frequently small the inhibitory effect on NA and DA release can be increased by simultaneous blockade of the respective autoreceptor. There are even examples of H3 heteroreceptors which could only be identified if the respective autoreceptor was blocked3 12,36. 

Heteroreceptors (HRs), like autoreceptors, can either suppress (inhibitory autoreceptors such as the tt2-adrenergic) or enhance the release of neurotransmitters. They are termed heteroreceptors since they are activated by neurotransmitters (e.g. norepinephrine) different from those produced by the nerve on which they are located (e.g. serotonergic). There might be numerous different heteroreceptors that bind various neurotransmitters on a single nerve. Table 1.2 summarizes some of the main modulating mechanisms relevant to intact functioning of the presynaptic nerve. Psychotropic medications can either enhance or suppress many of the major processes or modulatory events listed in this chapter. - ... 

Blockade of monoamine receptors (pre- and postsynaptic, or both). Some of these are presynaptic inhibitory auto/heteroreceptors (e.g. tt2 -adrenergic), which, when blocked, cause the presynaptic neurons to release more neurotransmitter to the synaptic cleft. Postsynaptic blockade of various receptors modulates cellular activities and is presumably responsible for the antidepressive effects. 

Studies conducted decades ago demonstrated various alterations in pre- and postsynaptic receptors that were thought to be associated with the development of major depressive disorder. Among these were upregulation of presynaptic inhibitory auto/heteroreceptors such as the a2-adrenergic, decreased synaptic concentrations of both norepinephrine and serotonin (see Section 1.1), and upregulation of postsynaptic receptors, especially the Pi-adrenergic. Moreover, it was even demonstrated that antidepressant treatment was associated with further alterations in these abnormal parameters (e.g. increases in... 

HTia,2a Serotonergic receptor subtypes a2-ADR Presynaptic inhibitory auto/heteroreceptor... 

---