Detail of "142569-99-1"

Reference

Evidence that morphine tolerance may be regulated by endothelin in the neonatal rats

Evidence that morphine tolerance may be regulated by endothelin in the neonatal rats. Puppala, Bhagya L.; Matwyshyn, George; Bhalla, Shaifali; Gulati, Anil ( Department of Pediatrics and Neonatology, Advocate Lutheran General Children's Hospital, Park Ridge, IL, USA). Biology of the Neonate, 86(2), 138-144 (English) 2004 S. Karger AG. CODEN: BNEOBV. ISSN: 0006-3126. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 2 Opioids are widely used in the neonatal intensive care units for analgesia and sedation. Management of tolerance and withdrawal symptoms in neonates remains a major challenge.Several reagents with their cas registry numbers 57-27-2 and 142569-99-1 are used here. The present study investigates the involvement of a central endothelin (ET) mechanism in the development of tolerance to morphine in neonatal rats. Pregnant female rats were rendered tolerant to morphine and rat pups were delivered at term by cesarean section. The affinity (Kd) and d. (Bmax) of ET receptors was detd. by [125I]ET-1 binding in the brains of neonatal rats. Changes in G-protein stimulation were detd. in placebo and morphine-tolerant neonatal rats by [35S]-guanosine-5'-o-(3-thio)triphosphate ([35S]GTPgS)-binding assay. Morphine tolerance did not affect the characteristics (affinity and d.) of the ET receptors in the neonatal rat brains. Morphine as well as ET-1 produced significantly lower (p < 0.05) maximal stimulation of [35S]GTPgS binding in morphine-tolerant neonatal rats compared to the placebo group. The ETA receptor antagonist, BMS182874, produced significantly higher stimulation of G proteins in the morphine-tolerant compared to the placebo group. The ETB receptor agonist, IRL1620, produced a similar effect in both placebo and morphine tolerant rats. This is the first report indicating the involvement of the G-protein-coupled ETA receptor in neonatal morphine tolerance. .