Aims: Yohimbine has been shown to modulate the pharmacological actions of opioid drugs in a way that could be of potential therapeutic interest. This work tries to study if this interaction involves the impairment of opioid receptor activation at the cellular level by studying the effects of morphine and yohimbine on NG108-15 neuroblastoma x glioma hybrid cells.
Main methods: [(35)S]GTPγS binding assays were performed to study δ-opioid and α(2B)-adrenoceptor activation by opioid and adrenoceptor agonists in the presence and absence of yohimbine. The effect of morphine was also studied after 6 h pre-incubations with morphine, yohimbine and combinations of these drugs taking into account previous results showing an interaction between both drugs in these conditions. Forskolin-induced cAMP accumulation was also studied by immunoassay in cells incubated with morphine for 6 h in the presence and absence of naloxone and yohimbine.
Key findings: Yohimbine behaved as a competitive antagonist/inverse agonist on α(2B)-adrenoceptors but did not modify G-protein activation by morphine, either in acute conditions or after 6 h of incubation. However, morphine-induced inhibition of cAMP accumulation was prevented both by naloxone and yohimbine when these drugs were present in the incubation medium.
Significance: Yohimbine seems to desensitise adenylate cyclase to the inhibitory effect of opioid-activated G proteins. This cellular effect could underlie the antagonistic actions of yohimbine on many pharmacological effects of the opioid both in vitro and in vivo.
Copyright © 2011 Elsevier Inc. All rights reserved.