Download Diapositivo 1

Turma 5 e 6:
Diana Silva
Daniela Silva
24 de Novembro de 2009
Filipa Nunes
Filipe Mira
Objectives

Characterize each type of opioid receptors by
explaining the preferential endogenous ligand;

Explain how the reaction processes using a
specific example;

Talk about dependency and its relation with the
opioid receptors.
Opioid Receptors

Belong to the superfamily of seven transmembranespanning G protein-coupled receptors.

Are key elements in a regulatory system.

Allow opioids outside the cell to modify intracellular
events and alter cell function.

Are divided into three types: mu, kappa and delta.
Receptor
Where is produced
Where is expressed
Effect
Agonist
μ
Lungs
Thalamus
Intestines
Pain, breathing, nausea
Adrenals
and vomiting areas in
Kidneys
the brain
Spleen
Supraspinal
analgesia
Bradycardia
Ventilatory
depression
Hypothermia
Euforia
Dependence miosis
ß endorphin
Dynorphin A1-13
Morphine and
derivates
δ
Lungs
Stomach
Intestines
Splean
Kidneys
Adrenals
Sexual organs
Heart
Cerebral cortex
Hippocampus
Olfatory tubercle
μ modulation
Analgesia
Ventilatory
depression
Leu-enkephalin
ß endorphin
Dynorphin A1-8
κ
Spinal
Thalamus
Hypothalamus
Cerebral cortex
Brain
Heart
Spinal analgesia
Ventilatory
depression
Sedation
Miosis
Dynorphin
Morphine
Nalbuphine
Drug Liking
Opioid molecules
Basic life functions
(e.g.: eating)
same biochemical brain processes
Feelings of pleasure
The Opioid Receptors
In a normal state
• Normally, natural opiatelike chemicals produced by the body link to mu
opioid receptors on the surface of neurons.
• This activates an enzyme that converts ATP into cAMP (cyclic adenosine
monophosphate)  production of NA (noradrenaline)
• Normal levels of alertness and respiration
Normal production of NA, no external opioids
The Opioid Receptors
After linkage of an opioid drug to the Mu receptor:
• The enzyme that converts ATP into cAMP is inhibited.
• cAMP is less produced.
• Less NA is released.
• Effects of sedation appear (alertness and breathing frequency drop)
After linkage of na opioid to the Mu receptor
The Opioid Receptors
After repeated opioid exposure:
• The neuron increases its supply of enzymes and ATP molecules.
• It produces enough cAMP to offset the inhibitory effect of the drug.
• Releases almost the same amounts of NA even though the drug is present.
• The individual doesn’t experience the same intensity as in early stages.
Repeated exposure to opiods
The Opioid Receptors
When the drug is discontinued:
• The inhibitory impact is lost.
• The neuron operates at normal efficiency but with more enzymes and more cAMP
production out of ATP.
• More cAMP leads to the release of more NA.
• Over release of NA  symptoms of withdrawal (jitters, anxyety, cramps, etc)
After discontinuing the drug
Opioid Tolerance
 The
need to take higher and higher dosages of drugs to
achieve the same opioid effect.
Brain neurons are naturally
“set” to release enough DA in
the NAc
Normal level of pleasure
Opioid Tolerance
Heroin links to mu receptors
Dopamine transporter is blocked
Dopamine
accumulates in the
synaptic cleft
Pleasure signals are
continued given
With repeated heroin use,
the brain responds to these successive large DA releases by increasing the
number and strength of the brakes on the VTA DA neurons, inhibiting the
neurons’ resting DA release.
Opioid Tolerance
Neurons’ resting DA release are inhibited
Dependent addict
wants more heroin
On the other hand, when he stops to
consume , a state of DA deprivation
will result, manifesting in dysphoria
and other withdrawal symptoms.
Reduction of normal DA release
Opioid Dependency
Because of…
 Withdrawal symptoms;
 The need of having pleasure;
 Environmental issues.
Bibliography
“Revista Portuguesa de Cardiologia”, Artigo de Revisão, SARAIVA Joana, et
al, publicação de Julho 2004, pp. 1317 – 1333.
http://www.aued.org/archivos/arti/roeye.htm
http://www.ff.up.pt/toxicologia/monografias/ano0708/g15_morfina/mecanismo_de_
accao.htm
http://www.ncbi.nlm.nih.gov/pubmed/15189164
http://www.nida.nih.gov/pdf/perspectives/vol1no1/03perspectives-neurobio.pdf
http://www.opioids.com/receptors/index.html
http://www.praticahospitalar.com.br/pratica%2042/pgs/materia%2014-42.html