Heteroreceptor/autoreceptor interaction

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. 

Presynaptic receptors, when located on the same terminals, may interact with one another (see Schlicker and Gothert 1998 Trendelenburg et al. 2003). Such cross-talk also occurs between presynaptic D2-like heteroreceptor on noradrenergic neurons and the presynaptic (X2-autoreceptors inhibition by one narrows the scope for inhibition by the other (Jackisch et al. 1985 see also 1.2.3, 1.2.5 and 1.3.3). 

Like D2-like heteroreceptors (Section 2.4), the H3 heteroreceptors on noradrenergic terminals may interact with terminal 0G2 autoreceptors preactivation of one receptor attenuates the effect obtainable by activation of the other (see Schlicker and Gothert 1998). 

Blockade of dopamine autoreceptors increased the extent of H3 receptor-mediated inhibition of dopamine release in mouse striatal slices this another example of an autoreceptor/heteroreceptor interaction (Schlicker et al. 1993 compare Sections 2.4, 3.3, 4.3). 

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... 

Intercellular communication in the nervous system is typically mediated through synaptic transmission via the release of neurotransmitters and their subsequent binding to specific receptors. The transmitter-receptor interaction then elicits changes in ion channel permeability and/or second messenger formation in the innervated cell. Neurotransmitters can also interact with receptors located on the presynaptic terminal (either autoreceptors, which are activated by the same transmitter, or heteroreceptors, which are activated by a different transmitter released by a different neuron) to regulate the presynaptic function, often by influencing neurotransmitter release. Termination of synaptic neurotransmission depends upon the removal of neurotransmitter molecules from the synaptic cleft by either enzymatic degradation or by reuptake into the presynaptic terminal. 

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