1. Neuropeptide hormones

2. Neuropeptides: Differ in synthesis Differ in metabolism
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.

4. Neuropeptides:
Precursor peptide and
“coding regions”

5. Neuropeptide structure

6. Neuropeptide
Receptors:

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

8. Selectivity and overlap

9. 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:
Neurotensin
Adrenaline:
Serotonin:
TRH
Purpose?
To regulate release of classic transmitter
To modulate action of classic transmitter
at postsynaptic receptor
… or is it the other way around?

10. Opiates and Opioids Opiate: ANY pharmacologially active
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
Codeine (1804)
Dextromethorphan
(1958)

11. Mu (μ) receptor Kappa (κ) receptor
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.

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

13. Opioid Receptors
(1983 Classification)

14. β-endorphin Met5-enkephalin Dynorphin A
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-Glu
β-endorphin
H-Tyr-Gly-Gly-Phe-Met-OH
Met5-enkephalin
Dynorphin A

15. POMC products

16. Discovery of opioid receptors in brain
Solomon Snyder
( )
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
( )
Neuroscientist
Discovered release of endogenous
opioids in the brain in response
to painful stimuli, 1975

17. Opioid receptor actions

18. Μu receptor actions

19. Distribution of
opioid neurons
and terminals

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

21. Magnocellular System
Parvocellular System

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

23. Pathway for reward-related learning

24. 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?

25. 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.

27. Larry R. Young