Identification of a novel Na+- and Cl−-coupled transport system for endogenous opioid peptides in retinal pigment epithelium and induction of the transport system by HIV-1 Tat

Abstract

The endogenous opioid peptides enkephalins, dynorphins and endorphins consist of five or more amino acids. These peptides participate in a multitude of biological functions in mammalian cells by interacting with different subtypes of opiate receptors located on the plasma membrane and in the nucleus. Here we report on the identification of a new peptide transport system in the human retinal pigment epithelial (RPE) cells that transports a variety of endogenous opioid peptides with high affinity. We identified this novel, hitherto unrecognized, transport system when we were analysing the differential effects of Tat, the transacting factor encoded by HIV-1, on various transport processes in RPE cells. This transport system is markedly induced by Tat. This opioid transport system is energized by transmembrane Na+ and Cl− gradients and is distinct from any of the previously identified transport systems for opioid peptides in mammalian cells. Free amino acids, dipeptides, tripeptides and non-peptide opiate receptor antagonists are excluded by this newly identified transport system. The affinities of endogenous opioid peptides for this system are in the range of 0.4–40 μM. The identification of the high-affinity Na+- and Cl−-coupled transport system in mammalian cells that is specific for endogenous opioid peptides and is induced by HIV-1 Tat is of significance not only to the biology of opioid peptides but also to the pathology of HIV-1 infection in humans.