Lecture_5-Neuropeptides_and_Hormones-4_slides - 1 Lecture...

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Unformatted text preview: 1 Lecture 5: Neuropeptides and Hormones Lecture 5: Objectives-Neuropeptides Define peptide and contrast with neuropeptide Compare and contrast the synthesis, storage and release of neuropeptides with those of the classical neurotransmitters (e.g., dopamine or serotonin; will see next lecture) Describe how N terminal acetylation and C-terminal modifications can affect the activity of the neuropeptide Describe the difficulties faced by neuropeptide pharmacologists regarding the design of selective agonists and antagonists for neuropeptide receptors Discriminate between opiates and opioids Compare and contrast the three main classes of opioid peptides in terms of their precursors, and receptor preferences Describe the major intracellular signaling pathway used by opioid receptors Describe the mechanisms of action of morphine, heroin, oxycodone, codeine, naloxone and naltrexone and explain how these drugs impact addiction by affecting dopamine transmission within the nucleus accumbens Explain how by affecting dopamine release in the nucleus accumbens, kappa agonists might lead to dysphoria Peptide Neurotransmitters or Neuropeptides-small proteins, made up of the 20 amino acids; joined by peptide bonds-neuropeptide: peptides that serve as neurotransmitters; can also serve as hormones 2 Neuropepetide Synthesis 1: neuropeptides are encoded by genes; propeptides ; regulated like any other protein in the body 2: Pro-peptide RNA translocates to the ER, guided by a signal peptide 3: signal peptidase cleaves bond between the propeptide and signal peptide propeptide 4: Propeptide is released from the ribosome and undergoes extensive posttranslation modification to become the active neuropeptide (cleavages and modifications at specific amino acid residues) Processing of POMC (proopiomelanocortin) 1: The POMC gene encodes the propeptides for a number of active neuropeptides incl. ACTH, - endorphin and melanocyte- stimulating hormone or MSH ( prepropeptide ) 2: The prepropeptide is translocated to the ER where it is translated into propeptides 3. The propeptides are processed by prohormone convertases 1 and 2 (PC1 and PC2); step-wise reaction, cleaving certain dibasic residues (e.g., Lys-Arg; Lys-Lys, Arg-Arg & Arg-Lys) smaller peptides with Lys and Arg at their N- and C-termini 4. carboxypeptidase E (CPE) and aminopeptidase remove these basic residues 1 2 3 Processing of POMC (proopiomelanocortin) 5: N-terminal acetylation via N- acetyltransferases can occur which regulates the activity of the neuropeptide-the effect of acetylation depends upon the particular peptide being processed: a) -MSH activity is increased by N-terminal acetylation b) endorphin activity is decreased by N- terminal acetylation 6: Amidation of glycine on C- terminus can occur via PAM NOTE: the specific neuropeptides synthesized from a prepropeptide gene depend upon the tissue because different tissues contain different prohormone convertases or CPE 3...
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This note was uploaded on 09/09/2011 for the course PSY 115 taught by Professor Staff during the Spring '11 term at UCSB.

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Lecture_5-Neuropeptides_and_Hormones-4_slides - 1 Lecture...

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