Opioid inhibition and desensitization of calcium channel currents in rat dorsal root ganglion neurons

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 270; no. 2; pp. 466 - 474
• Main Authors: Nomura, K, Reuveny, E, Narahashi, T
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.08.1994
• Subjects: Analgesics - pharmacology; Animals; Baclofen - pharmacology; Calcium Channel Blockers; Cyclic AMP-Dependent Protein Kinases - drug effects; Enkephalin, Ala-MePhe-Gly; Enkephalins - pharmacology; Ganglia, Spinal - drug effects; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology; Neurons - drug effects; Protein Kinase C - drug effects; Rats; Rats, Sprague-Dawley
• ISSN: 0022-3565; 1521-0103

The mu-opioid [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) inhibited the high voltage-activated calcium channel currents of neonatal rat dorsal root ganglion neurons in a voltage-dependent manner. The low voltage-activated currents were not affected by DAMGO. The inhibitory effect was eliminated by pretreatment of the cell with pertussis toxin, indicating that the receptor was coupled with the pertussis toxin-sensitive G protein. Although the DAMGO inhibition occurred quickly, it was relieved gradually during the 5-min application of DAMGO. The recovery from desensitization after washout of DAMGO was very slow. Pretreatment of the cell with 1 microM DAMGO for 18 hr induced almost complete tolerance to the agonist. GTP-gamma-S also inhibited the high voltage-activated calcium channel currents mimicking DAMGO inhibition and the inhibition diminished during continuous application, suggesting that desensitization could occur without receptor stimulation by the agonist. Baclofen caused a similar inhibition and desensitization to those by DAMGO, and the inhibition by the subsequently applied DAMGO was attenuated. Thus, desensitization by these distinct receptor agonists is heterologous. Modulation of G proteins which are coupled with these agonists may be involved in the desensitization process.