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Neuropeptide hormones

Neuropeptide hormones. Neuropeptides: Differ in synthesis Transmitter is made from gene transcription and posttranslational cleavage of precursor polypeptide. Differ in metabolism Peptidases cleave the transmitter at different amino acid junctions, rendering it inactive.

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Neuropeptide hormones

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  1. Neuropeptide hormones

  2. Neuropeptides: • Differ in synthesis • Transmitter is made from gene • transcription and posttranslational • cleavage of precursor polypeptide. • Differ in metabolism • Peptidases cleave the transmitter • at different amino acid junctions, • rendering it inactive.

  3. Neuropeptides: Precursor peptide and “coding regions”

  4. Neuropeptide structure

  5. Neuropeptide Receptors:

  6. Neuropeptides: Often found co-localized with “classic” neurotransmitters. Phylogenically old class of transmitter substance. Found in neurosecretory, endocrine, and neural cells.

  7. Selectivity and overlap

  8. Neuropeptides coexist with other neurotransmitters Noradrenaline: Galanin Enkephalin Neuropeptide Y GABA: Somatostatin (in hippocampus) Cholecystokinin Neuropeptide Y (in arcuate nucleus) Acetylcholine: VIP Substance P Dopamine: Cholecystokinin Neurotensin Adrenaline: Neuropeptide Y Neurotensin Serotonin: Substance P TRH Enkephalin Purpose? To regulate release of classic transmitter To modulate action of classic transmitter at postsynaptic receptor … or is it the other way around?

  9. Opiates and Opioids Morphine (1802) Diacetylmorphine or Heroin (1870) Opiate: ANY pharmacologially active alkaloid derived from opium. Induce “narcosis” (sleep) and analgesia. Opioid: ANY non-alkaloid substance that induces similar effects, AND competes for occupancy at opioid receptors Dextromethorphan (1958) Codeine (1804)

  10. Opiate Receptors (1976 Classification) Morphine Ketocyclazocine Mu (μ) receptor Kappa (κ) receptor Both drugs induced analgesia but did not displace one another. Morphine induced sleep, but ketocyclazocine induced psychosis.

  11. Discovery of opioid peptides Hans Kosterlitz (1903-1996) Physiologist Discovered enkephalins, 1975 Choh Hao Li (1913-1986) Biochemist Discovered endorphins,1975 (and a host of other neuropeptides) Avram Goldstein (1920 - ) Psychiatrist Proposed opioid peptides as neurotransmitters, 1978 Enkephalins (1975) Endorphins (1975) Dynorphins (1978) Endomorphans (1985) Orphinans (1989) Morphiceptin (from ß-casein; 1949)

  12. Opioid Receptors (1983 Classification)

  13. Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-GluTyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu β-endorphin H-Tyr-Gly-Gly-Phe-Met-OH Met5-enkephalin Dynorphin A

  14. POMC products

  15. Discovery of opioid receptors in brain Solomon Snyder (1938 - ) Neuroscientist Co-discovered opioid receptors in brain with Candace Pert, 1975 Candace Pert (1945 – 2013 ) Pharmacologist Co-discovered opioid receptors in brain with Sol Snyder, 1975 Huda Akil (1945 - ) Neuroscientist Discovered release of endogenous opioids in the brain in response to painful stimuli, 1975

  16. Opioid receptor actions

  17. Μu receptor actions

  18. Distribution of opioid neurons and terminals

  19. Oxytocin and Vasopressin 2 Cell groups: Magnocellular neurons project to the posterior pituitary Parvocellular neurons project to the rest of the brain

  20. Magnocellular System Parvocellular System

  21. Oxytocin is critical for sexual and parental bonding in many species. Oxytocin binding CeA VMH Sexually-experienced male rat Sexually-inexperienced male rat

  22. Pathway for reward-related learning

  23. Prairie Vole Montane Vole Microtus ochrogaster Microtus montanus Display “monogamy” in terms of Do not show alloparental care or alloparental care and mate choice. mate choice. What differs these genetic “cousins” from one another?

  24. Oxytocin and Vasopressin Prairie vole males have significantly more V1A receptor in the vental palladum relative to Montane vole males. This system is related to detection of MHCs, and controls motor output in response to dopamine signals from the nucleus Accumbens.

  25. Larry R. Young

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