We are interested in drug abuse, specifically morphine and methadone, by pregnant women and the effect that this drug use has on the respiratory function of their infants. Clinical data indicate that children born to drug-abusing mothers are oftentimes born prematurely, underweight, and most importantly may have acute respiratory depression followed by hyperventilation and acid-base disturbances. We are interested in determining whether the guinea pig is an appropriate model for studying opioid-induced respiratory depression of the neonate after chronic in utero exposure to the opioid analgesics methadone and morphine. The guinea pig is a more appropriate model for the human neonate based upon the respiratory and molecular data, as well as the maturity of the guinea pig at birth compared with the immaturity of the rat or the mouse pup. The goal of this report is to focus on the molecular pharmacology aspects of the mu opioid receptor (MOP) in vitro. In this project, we cloned the cDNA for rat and guinea pig MOP (Smith et al, 2004) into the mammalian expression vector pcDNA3.1. The DNA was sequenced and analyzed to show the homology of these two clones. The functionality of the cloned rat and guinea pig-MOP were analyzed when expressed in vitro in Chinese hamster ovarian cells. We describe the characterization of these mu opioid receptors using 3 H-diprenorphine saturation and competition ligand binding assays, and opioid-stimulated 35 S-GTP-γ-S binding data. The present data show that the guinea pig and rat MOP possess similar functional characteristics in these two assays, thereby making guinea pigs an acceptable model for the human MOP.
Supported in part by HD46420 and DA007912.
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