Opioid Receptors

Opioid Receptors

• There are three known types of receptors for opioid analgesics: μ, κ, and δ.
• κ-Opioid receptors are involved in analgesia, but also produce nausea and dysphoria (sadness, irritability, anxiety).

δ-Opioid Receptors

• δ-Receptor activation produces analgesia and may be related to seizures.
• Endogenous ligands for the δ receptor are the enkephalins.
• Until recently, there were few pharmacological tools for studying δ receptors, limiting understanding of their function.

δ-Receptor Function

• Exogenous ligands that activate δ receptors mimic the phenomenon of 'ischemic preconditioning', protecting downstream tissues from permanent interruption of blood supply.
• In rat models, introduction of δ-active ligands results in significant cardioprotection.

Opioid Receptors and Ligands

• Opioid receptors are a group of G-protein coupled receptors with opioids as ligands.
• Endogenous opioids include dynorphins, enkephalins, and endorphins.
• Opioid receptors share ~40% identity with somatostatin receptors (SSTRs).

μ-Receptor Activation

• Activation of the μ receptor by an agonist like morphine causes analgesia, sedation, reduced blood pressure, itching, nausea, euphoria, decreased respiration, miosis (constricted pupils), and decreased bowel motility leading to constipation.
• Effects like sedation, euphoria, and decreased respiration tend to disappear with continued use as tolerance develops.
• Analgesia, miosis, and reduced bowel motility tend to persist with little tolerance development.
• Tolerance develops to different effects at different rates due to activation of different μ-receptor subtypes.
• μ1-Receptors block pain, while μ2-receptors cause respiratory depression and constipation.