Abstract:
:The alpha(2)-adrenoceptor antagonist yohimbine is known to interact with the effects of opioid receptor agonists in vivo, and thus could modulate the action of morphine-like analgesics. The focus of the present work was to further study these interactions in a cell culture endowed with opioid and alpha(2)-adrenoceptors in order to know if they could happen at the cellular level. In a first step, incubation with morphine (10microM) or the delta opioid agonist DPDPE (1microM) for 6h was shown to decrease the reduction of (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) by NG108-15 neuroblastomaxglioma hybrid cells in a naloxone-sensitive manner, thus showing that the opioids affect the redox status of the cells in a delta receptor-mediated way. Further experiments with 2-24h incubation periods were subsequently performed with morphine 0.1microM, 10microM and 1mM and several tests to confirm the effects on metabolism (MTT, Alamar Blue tests) to examine the potential toxic consequences (neutral red test, trypan blue exclusion assay, LDH test, caspase 3/7 activity) and to study the potential effect of yohimbine on morphine toxicity. These studies confirmed that incubation with morphine (0.1microM and 10microM) affected to a similar extent the redox status of the cells, an effect that did not translated into significant cell death and was transient since completely disappeared after 24h of incubation. Morphine 1mM was much more toxic than the lower concentrations. Yohimbine effectively prevented the effects of the lower concentrations of morphine when added to the incubation medium at 10microM, a concentration devoid of significant toxicity. It seems that the exposure to pharmacologically relevant concentrations of morphine gives rise to short-term metabolic alterations of NG108-15 cells mediated by delta receptors and also sensitive to alpha(2)-adrenoceptor blockade; therefore, the interactions previously described in vivo between opioid and alpha(2)-adrenoceptor ligands do not necessarily require the presence of functional neuronal networks and they could happen at the cellular level.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Polanco MJ,Alguacil LF,Albella B,Segovia JC,González-Martín Cdoi
10.1016/j.toxlet.2009.05.010subject
Has Abstractpub_date
2009-09-10 00:00:00pages
115-20issue
2eissn
0378-4274issn
1879-3169pii
S0378-4274(09)00259-8journal_volume
189pub_type
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