Neurobiology presentation, 2016.10.20. Halász Olivér Ferreira, et al. The Journal of Neuroscience, 2015 Neuropeptides target metabotropic receptors

Neuropeptides Sytnthesized from precursors produced in the RER of the pre-synaptic neuron Transported in vesicles to the axon-terminal Cleavage of the protein -> multiple peptides (same/different kinds) Secreted with exocytosis (Ca-ion and ATP required) May be modified in the extracellurar space (another cleavage) Bind exclusively to metabotropic receptors Not recycled, diffused and hydrolyzed Affect gene expression, local blood flow, synaptogenesis, glial cell morphology Some peripherical peptide hormones also function as NTs in the nervous system Often co-released with other neurotransmitters

Peptide families Tachykinins (e.g. Substance P, Neurokinin A – B) Opioid peptides (e.g. nkephalin, Endorphin, Dynorphin) Pancreatic polypeptide related (e.g. Neuropeptide Y, Peptide YY) Insulin family (e.g. Insulin, insulin-like growth factors) Gastrins (e.g. Gastrin, cholecystokinin) Secretins (e.g. Vasoactive intestinal peptide, glucagon) Neurohypophyseal hormones (e.g. Oxytocin, vasopressin) Release (inhibiting) (e.g. TRH, CRH, somaostatin) Feeding peptides (e.g. Neuropeptide Y, orexin, alpha-melanocyte stimulating hormone)

The target of NPs: Metabotropic receptors

Metabotropic receptors cAMP system

Metabotropic receptors cont. Incites ion-channel opening/closing or intracellural effects After the binding of NP (agonist) a conformation change takes place G-protein activation G-proteins can open and shut ion channels directly, or… Activate signaling cascades (second messenger system): 1 The cyclic AMP system, responsible for phosphorylation of proteins. 2 The phosphoinositol system, responsible for liberating calcium from cytoplasmic stores. 3 The arachidonic acid system, responsible for production of arachidonic acid metabolites. Much slower response than in ionotropic receptors (Other types of neurotransmitters can also bind to metab. receptors)

References: • D.Purves, G. J Augustine, D. Fitzpatrick, L. C Katz, A.-S. LaMantia, J. O McNamara, S. M. Williams. (2001). Neuroscience, 2nd edition • https://en.wikipedia.org/wiki/Neuropeptide • http://clinicalgate.com/transmitters-and-receptors/ • From lecture notes: Dyck, R. (2010) Personal Communication • https://users.itk.ppke.hu/neurobiologia/LECTURES_2016- 2017_SEMESTER_1/5.%20WEEK/1.%20HANDOUT/Neurob_14.pdf • https://www.coursera.org/learn/medical-neuroscience/lecture/vvyfY/metabotropic- neurotransmitters-receptors-and-postsynaptic-mechanisms