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

Biology of the Neonate
Bhagya L PuppalaAnil Gulati

Abstract

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. 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 density (Bmax) of ET receptors was determined by [125I]ET-1 binding in the brains of neonatal rats. Changes in G-protein stimulation were determined in placebo and morphine-tolerant neonatal rats by [35S]-guanosine-5'-o-(3-thio)triphosphate ([35S]GTPgammaS)-binding assay. Morphine tolerance did not affect the characteristics (affinity and density) 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]GTPgammaS 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 ...Continue Reading

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Citations

Apr 1, 2007·Indian Journal of Psychiatry·Swapnil Gupta, Parmananda Kulhara
Jun 18, 2010·Canadian Journal of Physiology and Pharmacology·Mustufa BoxwallaAnil Gulati
Nov 11, 2008·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·David Calderón GuzmánHugo Juárez Olguín
Nov 19, 2005·Peptides·Bhagya L PuppalaAnil Gulati
Jul 26, 2005·Peptides·Richard J Bodnar, Gad E Klein
Jul 22, 2014·Cell Biology International·Ahmed M SalemHadeer A Aglan
Jun 8, 2006·Neurochemical Research·David Calderón GuzmánHugo Juárez Olguín
Mar 22, 2020·Journal of Clinical Medicine·Frederik C EnevoldsenMarcus Krüger

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