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ISSN 0185-3325 (Print)
Órgano Oficial del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz

2000, Number 2

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Salud Mental 2000; 23 (2)

Otro sistema de transmisión opioide en el cerebro de los mamíferos. Las endomorfinas y el receptor opioide mu Parte II

Leff P, Acevedo R, Valdés A, Martínez I, Morales A, Calva JC, Antón B

Language: Spanish
References: 47
Page: 36-41
PDF size: 158.55 Kb.


ABSTRACT

Several opioid peptides have been identified, cloned and subsequently characterized by pharmacological and molecular approaches. These peptides mediate a vast number of biological functions in discrete brain regions, where they activate the different opioid receptors subtypes referred to as mu, delta and kappa. These receptors belong to a class of Giprotein coupled membrane receptors being structurally defined by seven peptide transmembrane domains. Opiate drugs mainly mediate their analgesic, euphoric and rewarding effects by activating the mu-opioid receptor subtype. Besides the detailed description of the anatomical expression of each opioid receptor subtype throughout the CNS of mammals, opioid receptors reveal a distinct but overlapping distribution as well as a single pharma-cological profile. Moreover, opioid receptors activate a similar subcellular effector system, which involves a functional modulation of the adenylyl cyclase, protein kinases, phosphoinositide turnover as well as ion conductances such as calcium and potassium. Pharmacological studies related to the structure-activity relationships of the cloned opioid receptors expressed in heterologous cellular systems have revealed that natural occurring opioid peptides selectively bind with differential affinities to the different opioid receptor subtypes. Thus, enkephalins display a preferential binding to the deltaopioid receptor while dynorphins are considered the selective endogenous ligands for the kappa-opioid receptor. Furthermore, no endogenous peptide agonist ligands displaying high affinity binding for the m opioid receptor subtype have been identified. Recently, two novel endogenous opioid peptides referred to as endomorphins were isolated and cloned from the CNS of mammals. The pharmacological and functional properties of these two peptides have just begun. In line with these investigations, initial studies have shown that endomorphins display the highest affinity binding for the mu opioid receptor reported to date as well as a very potent and prolonged analgesic activity in rodents.


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