Endogenous opioids: Why do our brains make drugs?

 

The opiates

Opium poppy in history

Opium poppy, Papaver somniferum

Cultivated in Asia and Europe

Valued as analgesic (reduces perception of pain, no loss of consciousness)

Opium contains morphine , codeine, noscapine, papaverine, thebaine

Opium in 18th and 19th centuries - mother's friend, Opium Wars

codeine, morphine vs. heroin (semisynthetic) - search for ideal opiate

Synthetic antagonists

Biological effects: sedation, sleep aid, analgesia, antidiarrheal, pleasure

Opiate receptors

Radioactive ligand - synthetically marked, highly sensitive,

Tissue extracts

Several classes by pharmacology -

m: mediates morphine analgesia, pleasure responss in mice; binds enkephalin

k : endorphin?

d: deltorrphin, enkephalin?

The search for endogenous opioids

Endorphins: a (16), b (31), g (17), s (27)

Enkephalins: pentapeptides; thalamus and spine; fragment of endorphins

Dynorphin

Their synthesis

Pre-pro-opiomelanocortin

POMC gene expressed in anterior, intermediate lobes of pituitary gland

Primary protein a 285 amino acid

Undergoes differential processing to yield 8+ hormones

Processing depends on location of synthesis, stimulus.

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Cellular processing

Vesicle packaging

Secretion

CRH ==> secretion of ACTH, a variety of other peptides

CRH-stimulated secretion of ACTH, others mediated by adenylate cyclase,

increase in cAMP and PKA

Longer-term, CRH ==> a marked increase in POMC mRNA

Their mechanism of action

Structure:

Ion channels; neurons

Extracellular N-terminal region

Seven transmembrane domains

Intracellular C-terminal tail

G Protein coupling

Why are they there?

Pleasure pathway: limbic striatum

Normal part of positive behaviors: eating, exercise, sex

Endogenous opioids involved

Role in stress, immune function, depression,

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Other behaviors:

Alcohol

Nicotine

Opiate drugs: heroin, etc.

 

Alternatives:

Massage, hydrotherapy

Exercise, meditation, relaxation, humor

 

Placebos

Expectancy

Pill vs. shot vs. IV drip

 

You are always welcome to ask questions, both inside class and outside of it. My phone number is 335-7891 and my email address is alice-fulton@uiowa.edu .

I welcome suggestions for future topics.

November 1: Nutritional biochemistry: What is the rationale behind the food pyramid? How is it connected with our biological past? How does nutritional biochemistry help prevent and treat diseases such as coronary disease and adult diabetes?

December 6: Steroid Hormones: Estrogen, testosterone, and relatives - how are these derivatives of cholesterol made? How do they act? Should we be concerned about environmental estrogens and anabolic steroids?

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Precursor

Endogenous peptide

Amino acid sequence

Pro-opiomelanocortin

b-Endorphin

YGGFMTSEKSQTPLVTL-

FKNAIIKNAYKKGE

Pro-enkephalin

[Met]enkephalin

[Leu]enkephalin Metorphamide

YGGFM

YGGFL

YGGFMRF

YGGFMRGL

YGGFMRRV-NH2

Pro-dynorphin

Dynorphin A

Dynorphin A(1-8)

Dynorphin B

a-neoendorphin

b-neoendorphin

YGGFLRRIRPKLKWDNQ

YGGFLRRI

YGGFLRRQFKVVT

YGGFLRKYPK

YGGFLRKYP

Pro-nociceptin / OFQ

Nociceptin

FGGFTGARKSARKLANQ

Pro-endomorphin*

 

Endomorphin-1

Endomorphin-2

YPWF-NH2

YPFF-NH2