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Halász Viktor Olivér Neurobiology presentation 2016.10.20. Peptide transmitters targeting metabotropic receptors Neuropeptides The group of neuropeptides is a special type of neurotransmitter. They are synthesised in the form of protein precursors in the R.ER of the pre-snynaptic cell and transported in vesicles (anterogradly) to the axon terminal. Before being “ready for use”, they go through maturation processes which involve the cleavage of the precursor, resulting in multple neuropeptides. (The cleavage might even happen outside the cell, a bit later.) After exocytosis, they bind to the metabotropic receptors of the post-synaptic cell membrane, activating a kind of mechanism there. Neuropeptides are never recycled, instead, they are hydrolyzed back into amino acids. NPs are sometimes co-released with other eurotransmitters. Several families of neuropeptides exist (with different cateorizations), each cater to a variety of functions. Some of them play role in perception of pain, or responses to stress, while others affect social behaviour and pair bonding. More precisely/locally, they can regulate gene expression, local blood flow and synaptogenesis (among others). Metabotropic (G-protein coupled) receptors It may be targeted by both neuropeptides and other types of neurotransmitters. After the agonist has bounded to the receptor, due to the resulting comformation change of the receptor, the linked G-protein dissociates. Then, the G-protein can either directly, or indirectly activate different mechanisms in the cell. It can bind to a Na+ channel, opening the channel, resulting in the propagation of the depolarization wave in the postsynaptic cell. The indirect activation can happen in multiple ways, all of which involve one/more second messengers. The Cyclic AMP system results in the opening (closure) of the Na+ channel, thus propagating the depolarization. This involves Protein Kinase A as the effector enzyme and also GTP, ATP and cAMP. The Phosphoinositol and the Arachidonic acid systems both entail a complex activationl pathway, involving phospholipase C, Protein Kinase C, DAG and inositol phosphate. The last one opens up Ca2+ channels at the S.ER, therefore activating a series of Calcium-dependent enzymes. The arachidonic acid system is an important part of the inflammatory process signaling. The response time of the G-protein coupled receptor is much longer. References: D.Purves, G. J Augustine, D. Fitzpatrick, L. C Katz, A.-S. LaMantia, J. O McNamara, S. M. Williams. (2001). Neuroscience, 2nd edition From lecture notes: Dyck, R. (2010) Personal Communication https://www.coursera.org/learn/medical-neuroscience/lecture/vvyfY/metabotropic-neurotransmitters-receptors-andpostsynaptic-mechanisms https://en.wikipedia.org/wiki/Neuropeptide http://clinicalgate.com/transmitters-and-receptors/ https://users.itk.ppke.hu/neurobiologia/LECTURES_2016-2017_SEMESTER_1/5.%20WEEK/1.%20HANDOUT/Neurob_14.pdf