Subtypes of Guanine-Nucleotide-Binding Regulatory Proteins at the Locus coeruleus Involved in Fentanyl-Induced...

Previous results from our laboratory have established that the G(o) subtype of guanine nucleotide (GTP)-binding regulatory protein at the locus coeruleus (LC) may participate in the elicitation of muscular rigidity by fentanyl. The present study further examined the involvement of other subtypes of GTP-binding regulatory proteins at the LC in this process, using Sprague-Dawley rats anesthetized with ketamine (120 mg/kg, i.p., with 30 mg/kg/h i.v. infusion supplements) and under mechanical ventilation. Intravenous administration of fentanyl (100 &mgr;g/kg) induced a significant increase in electromyographic signals recorded from the sacrococcygeus dorsi lateralis muscle. Power spectral analysis revealed that this was accomplished by a decrease in the mean power frequency and an increase in the root mean square values of the signals. The above responses were appreciably antagonized by pretreating animals with bilateral microinjection into the LC of pertussis toxin (80 or 160 fmol), N-ethylmaleimide (16 pmol) or 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (100 or 200 fmol); but not by cholera toxin (120 or 240 fmol), forskolin (240 or 480 pmol) or N-ethylmaleimide at a higher dose (32 pmol). These results suggest that, in addition to G(o) protein, fentanyl-induced muscular rigidity may also involve other pertussis toxin-sensitive GTP-binding regulatory proteins, possibly G(i) and G(p) subtypes, in the signal transduction processes following activation of &mgr;-opioid receptors at the LC. Copyright 1995 S. Karger AG, Basel