Opioid receptors signal transduction mechanisms

Jordan B, Devi LA. Molecular mechanisms of opioid receptor signal transduction. Br J Anaesth 1998 81(1) 12-19. 

Signal Transduction Mechanisms, 342 3.2.3Characterizationof Opioid Receptors,... 

Consistent with the sequence similarities between the ORLl and opioid receptors, activation of the ORLl receptor triggers the same signal transduction mechanisms as used by the opioid receptors. Thus activation of ORLl receptors inhibits both forskolin-stimulated adenylyl (yclase and currents and activates several other effectors, including inward rectifying channels, protein kinase C, mitogen-activated protein kinase (MAP kinase) and phospholipase C (see Ref 89 for a review). 

Signal transduction mechanism for mu, delta, and kappa receptors is via the Gi/o proteins. Thus, the activation of the ensuing opioid receptors is directly associated with the G protein to an inhibition of the critical adenylate cylase activity. Consequently, the ultimate lowering in cAMP production essentially affords an efflux of ions, and finally gives rise to hyperpolarization of the nerve cell. ... 

The signal transduction mechanism for p, 5, and k receptors is through Gi/o proteins. Activation of opioid receptors is linked through the G protein to an inhibition of adenylate cyclase activity. The... 

Fig. 3 Mechanisms involved in the opioid ( r, 8, k, ORLi) and neuropeptide Y (Y2) receptor-mediated inhibition of exocytotic transmitter release. Following activation of the respective receptor and Gi/0 (1), three signal transduction pathways are possible, namely inhibition of voltage-dependent Ca2+ channels (2), opening of K+ channels (3), and a direct inhibitory effect on the vesicle release machinery (4). Glossary — > - leading to => - ion flux => - action potential Vm - membrane potential (+) and mean stimulatory and inhibitory effect, respectively.

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