engleski

Signalling promiscuity of the metabotropic neurotransmitter receptors : are there any functional consequences

Many neurotransmitter receptors are metabotropic, i.e., belong to the superfamily of G-protein coupled receptors and are promiscuous in regard to their intracellular signalling - they couple to multiple signalling pathways, either simultaneously, or, at least in vitro, alternatively. The simultaneous coupling implies activation of at least two different signalling pathways at the same time, one major, and one or more minor pathways, including interactions with ion channels. Our knowledge about functional significance of this signalling diversity is restricted to a limited number of cases. Interactions with ion channels seem undoubtedly important for the function of some receptor types in electrically-excitable cells and tissues and airway smooth muscle. The interactions with the signalling pathways controlling mitogenesis (Ras-MAPK and MEKK/JNK) have been clearly demonstrated in artificial in vitro models and account for the in vitro effects of neurotransmitter receptors on cell proliferation and differentiation. There is circumstantial evidence that these events may as well occur in vivo, at least in some tissues and under certain conditions. The alternative coupling implies that a particular receptor, in a particular cell, may switch from one to another major signalling system. This mode of signalling promiscuity has been clearly demonstrated in vitro, and suggests that a particular receptor, in a particular cell, could change its function. As yet, there is only circumstantial evidence that the signalling and functional receptor switch might occur in vivo. However, such a possibility is extremely intriguing and deserves attention, because if it is to be proven in vivo it could significantly change our view on basic biological concepts, such as those of neuronal plasticity, rational pharmacotherapy and pathophysiology of some diseases.

neurotransmitter receptors; G-proteins; intracelullar signalling; receptor function

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