Eastern Kentucky University
Computational Studies of the Human Mu and Kappa Opioid Receptor
Institution
Eastern Kentucky University
Faculty Advisor/ Mentor
Debra Bautista
Abstract
Opioid receptors belong to the superfamily of G protein coupled receptors and are primarily responsive to opiates to produce analgesia, but also produce a variety of side effects. Opioid receptors are divided into three types “mu (µ), kappa (κ), and delta (δ)”. Each type can be further subdivided based on their pharmacological and physiological characteristics. Homology models of human µ and κ receptors were developed based on bovine rhodopsin. Each receptor binds to a selective and a nonselective agonist. Morphine acted on both receptors at similar positions. Morphine binds to serine residues at the same position on both receptors. Morphine also binds specifically with His 321 and Trp 320 residues on the µ receptor. At those same positions on the κ receptor, morphine binds with Tyr 313 and Tyr 312 residues, respectively. Therefore, it is apparent that relief of pain by morphine and the characteristic side effects produced are dependent on the residue located at a specific position on a specific opioid receptor. Morphine is more likely to provide analgesia, without induced side effects, when interacting with residues specific for to the µ receptor. It is conceivable that morphine is a non-selective agonist for the κ receptor and their interaction may be the determinant factor in whether or not adverse side effects occur.
Computational Studies of the Human Mu and Kappa Opioid Receptor
Opioid receptors belong to the superfamily of G protein coupled receptors and are primarily responsive to opiates to produce analgesia, but also produce a variety of side effects. Opioid receptors are divided into three types “mu (µ), kappa (κ), and delta (δ)”. Each type can be further subdivided based on their pharmacological and physiological characteristics. Homology models of human µ and κ receptors were developed based on bovine rhodopsin. Each receptor binds to a selective and a nonselective agonist. Morphine acted on both receptors at similar positions. Morphine binds to serine residues at the same position on both receptors. Morphine also binds specifically with His 321 and Trp 320 residues on the µ receptor. At those same positions on the κ receptor, morphine binds with Tyr 313 and Tyr 312 residues, respectively. Therefore, it is apparent that relief of pain by morphine and the characteristic side effects produced are dependent on the residue located at a specific position on a specific opioid receptor. Morphine is more likely to provide analgesia, without induced side effects, when interacting with residues specific for to the µ receptor. It is conceivable that morphine is a non-selective agonist for the κ receptor and their interaction may be the determinant factor in whether or not adverse side effects occur.