Presynaptic nicotinic receptors modulating neurotransmitter release in the central nervous system: functional interactions with other coexisting receptors.

The cross-talk between receptors represents an important mechanism of neurotransmission modulation and plasticity. It can occur by direct physical interactions as in the case of G protein-coupled receptor heterodimerization, or it may involve intracellular pathways. The facilitatory or inhibitory action of one receptor might therefore depend on the function of the other receptors coexisting on the neuron. Recent studies have shown that this phenomenon also concerns the nicotinic receptor subtypes. This review will focus on the coexistence and the functional interaction between the release regulating presynaptic nAChR and other receptors coexisting on the same axon terminals. Presynaptic nicotinic acetylcholine receptors in the Central Nervous System may interact with other metabotropic or ionotropic receptors producing an integrated response which, in turn, generates antagonistic or synergistic effects. The understanding of these interactions may allow a better evaluation not only of the pharmacological effects of nicotine, but also of the normal physiological role of the natural neurotransmitter acetylcholine.