Another opioid transmission system in the CNS of mammals. Endomorphins andopioid receptor mu. Part II.

Several opioid peptides have been identified, cloned and subsequently chara cterized by pharmacological and molecular approaches. These peptides mediat e a vast number of biological functions in discrete brain regions, where th ey activate the different opioid receptors subtypes referred to as mu, delt a and kappa. These receptors belong to a class of Gi-protein coupled membra ne receptors being structurally defined by seven peptide transmembrane doma ins. Opiate drugs mainly mediate their analgesic, euphoric and rewarding ef fects by activating the mu-opioid receptor subtype. Besides the detailed de scription of the anatomical expression of each opioid receptor subtype thro ughout the CNS of mammals, opioid receptors reveal a distinct but overlappi ng distribution as well as a single pharma-cological profile. Moreover, opi oid receptors activate a similar subcellular effector system, which involve s a functional modulation of the adenylyl cyclase, protein kinases, phospho inositide turnover as well as ion conductances such as calcium and potassiu m. Pharmacological studies related to the structure-activity relationships of the cloned opioid receptors expressed in heterologous cellular systems h ave revealed that natural occurring opioid peptides selectively bind with d ifferential affinities to the different opioid receptor subtypes. Thus, enk ephalins display a preferential binding to the deltaopioid receptor while d ynorphins are considered the selective endogenous ligands for the kappa-opi oid receptor. Furthermore, no endogenous peptide agonist ligands displaying high affinity binding for the m opioid receptor subtype have been identifi ed. Recently, two novel endogenous opioid peptides referred to as endomorph ins were isolated and cloned from the CNS of mammals. The pharmacological a nd functional properties of these two peptides have just begun, in line wit h these investigations, initial studies have shown that endomorphins displa y the highest affinity binding for the mu opioid receptor reported to date as well as a very potent and prolonged analgesic activity in rodents.