Development of cellular tolerance to racemic buprenorphine

CHED 1334

Chinmayee V Subban, subbanc@ohsu.edu, Michael Wallisch, wallisch@ohsu.edu, and George D Olsen, olsenge@ohsu.edu. Department of Physiology & Pharmacology, Oregon Health & Science University, L334 School of Medicine, 3181 SW Sam Jackson Park Rd, Portland, OR 97239
The methadone maintenance program is the standard of care for heroin addicted pregnant women. However, buprenorphine has been suggested to decrease neonatal abstinence syndrome in human infants compared to methadone. Respiratory depression in newborn babies is a major concern of all drug abuse treatment during pregnancy. The opioid-induced neonatal abstinence syndrome and respiratory depression are currently under examination in the guinea pig model in our laboratory. On the cellular level, opioid agonists induce tolerance which is manifested in desensitization, internalization, and down-regulation of the mu opioid receptor (MOP). In this work we compare the molecular pharmacology of morphine, the major metabolite of heroin, methadone, the current drug of treatment, and buprenorphine, a potential new treatment for drug addiction, in the guinea pig model. We used the cloned guinea pig mu opioid receptor stably expressed in Chinese hamster ovarian cells (CHO) to compare the effects of prolonged opioid exposure in vitro. Cells were treated in culture with each drug for up to 12 hours. Immediately after drug exposure MOP-containing membrane preparations were harvested and assayed for receptor binding and activation. 3H-diprenorphine receptor binding was used to compare the binding activities following opioid exposure. In addition, receptor activation was analyzed by 35S-GTPgammaS binding. Our results show the different effects of the three drugs tested on reduction of binding and decrease of activation of the mu opioid receptor after chronic opioid exposure.
 

Undergraduate Research Poster Session: Medicinal
2:00 PM-4:00 PM, Monday, March 26, 2007 Hyatt Regency Chicago -- Riverside Center, Poster

Division of Chemical Education

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007