Lecture_9-Neuropeptides_and_Hormones

(formerly orphanin identified in 1995 binds orl-1

Info iconThis preview shows pages 14–25. Sign up to view the full content.

View Full Document Right Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: (formerly orphanin) - identified in 1995; binds ORL-1 receptor; • has HYPERalgesic effects • Endomorphin has high affinity for receptor Opioid distribution in the brain varies by peptide, but all are prevalent in pain and reward pathways Distribution of opioid peptide-producing neurons • Distributed throughout the CNS • Heavily integrated in pain pathways and dopaminergic reward pathways Opioid Receptors have three major classes: (mu), (delta) and (kappa) • G protein-coupled and have 7 transmembrane spanning regions • Receptor classes have specificity for certain opioids • Each class has subtypes; these can vary dramatically in their effects, even when stimulated by the same ligand • Orphan receptor (ORL) was recently discovered and other receptors may also exist ( is not • Distribution in the CNS is broad but varies by receptor class • Intracellular activity can vary by class Opioid receptor distribution in the brain ORL1 ORL1 Opioid peptide cellular signalling is metabotropic and has three primary effects driven by Gi activation • Inhibit adenylyl cyclase – influence (inhibit) Na + influx – inhibit neurotransmitter release – inhibit stimulatory effects of other neurotransmitters • Open K + channels – increase movement of K + out of the cell – hyperpolarize the cell • Inhibit Ca ++ channels – decreased Ca ++ entry – inhibit neurotransmitter release Opioid receptor activation results in a number of different cellular responses -opioid receptors (MOR) -opioid receptor morphine G-Protein subunits • Named for m orphine affinity • Subtypes are 1 2 • . -endorphin has highest affinity • MOR activation produces effect similar to receptors (DOR) – Analgesia, euphoria (reward) – Blood pressure, gastrointestinal • Rats will self-administer MOR and DOR receptor agonists • But only MORs are implicated in tolerance and dependence • However, 2 receptors were recently found to play a role in nausea • High concentration in the thalamus, periventricular nuclei, periaqueductal grey and pituitary Opiate agonists are more practical for use in therapeutic (and recreational) settings • Opiates, extracted from opium, can be modified to alter their potency • Synthetic analogues are produced with goals of ideal potency & selective effects (minimal side effects and abuse potential) • Efficacy of opiate analogues correlates with their ability to: 1. Cross the BBB 2. Bind opioid receptors (affinity) 3. Resist metabolism to inactive metabolites • Selective effects are achieved by creating analogues structurally specific to a particular opioid receptor type NUBAIN FENTANYL MORPHINE A few opioid analgesics GABA neuron GABA neuron Dopamine neuron Dopamine neuron Undrugged On heroin/morphine 1 2 3 4 5 6 7 8 Hypothesized “pro-addictive” mechanism for certain mu agonists Opioid antagonists are also important therapeutics • Antagonists can bind opioid receptors with extremely high affinity and immediately...
View Full Document

{[ snackBarMessage ]}

Page14 / 32

(formerly orphanin identified in 1995 binds ORL-1 receptor...

This preview shows document pages 14 - 25. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online