In vivo modulation of G proteins and opioid receptor function by antisense oligodeoxynucleotides.
The work in our laboratory has been designed to characterize the transducer mechanisms coupled to neurotransmitter receptors in the plasma membrane. Particular attention has been paid to the physiological/pharmacological effects mediated by the opioid system. Antisense oligodeoxynucleotides have proved useful in correlating opioid receptor clones with those defined pharmacologically. The involvement of the cloned opioid receptors mu, delta, and kappa in analgesia has been determined by means of in vivo injection of ODNs directed to the receptor mRNAs. Using this strategy the classes of G-transducer proteins regulated by each type/subtype of opioid receptor in the promotion of antinociception have also been characterized. After displaying different patterns of binding to their receptors, opioids trigger a variety of intracellular signals. The physiological implications and therapeutic potential of these findings merit consideration.
Garzón
J
J
Department of Neuropathology, Cajal Institute, Madrid, Spain.
de Antonio
I
I
Sánchez-Blázquez
P
P
D000698:Analgesia / Q000379:methods*; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D020962:Heterotrimeric GTP-Binding Proteins / Q000187:drug effects* / Q000235:genetics; D007276:Injections, Intraventricular; D051379:Mice; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000235:genetics; D015398:Signal Transduction
D000700:Analgesics; D020319:Oligodeoxyribonucleotides, Antisense; D011957:Receptors, Opioid; D020962:Heterotrimeric GTP-Binding Proteins