In Vitro Interaction of Tetrahydrouridine with Key Human Nucleoside Transporters.

NDec is a novel combination of oral decitabine and tetrahydrouridine that is currently under clinical development for the treatment of sickle cell disease (SCD). Here, we investigate the potential for the tetrahydrouridine component of NDec to act as an inhibitor or substrate of key concentrative nucleoside transporters (CNT1-3) and equilibrative nucleoside transporters (ENT1-2). Nucleoside transporter inhibition and tetrahydrouridine accumulation assays were performed using Madin-Darby canine kidney strain II (MDCKII) cells overexpressing human CNT1, CNT2, CNT3, ENT1, and ENT2 transporters.

Mechanisms and therapeutic potential of inhibiting drug efflux transporters.

Introduction: The ATP-binding cassette transporters are among the largest transmembrane protein families in humans and are expressed in a wide variety of tissues. By promoting outward transport, they protect cells from the accumulation of undesirable substrates. This protection might lead to suboptimal concentration of chemotherapeutics in the tumor cells, resulting in therapy resistance and poor disease prognosis.

Effects of nociceptin and nocistatin on uterine contraction.

The presence and effects of nociceptin (N/OFQ) and nocistatin (NST) in the central nervous system have been reasonably well described, but less data are available on their peripheral functions. Besides their presence in several peripheral organs (white blood cells, airway, liver, skin, vascular and intestinal smooth muscles, ovary, and testis), they have been found in the pregnant myometrium in both rat and human. The level of their precursor prepronociceptin is elevated in the preterm human myometrium as compared with full-term samples, whereas it gradually increases toward term in the pregnant rat uterus.

Tocopherol inhibits the relaxing effect of terbutaline in the respiratory and reproductive tracts of the rat: the role of the oxidative stress index.

Aims: Reactive oxygen species play a role in the signal transduction of beta-adrenergic receptors. We investigated whether an antioxidant (tocopherol) can reduce the effect of terbutaline in beta-2-adrenergic receptor (β2-AR)-regulated smooth muscles.

Main Methods: Contractility of the tissues from nonpregnant (trachea) and 22-day-pregnant (myometrium and cervix) rats was investigated in an isolated organ bath.