A functional link between T-type calcium channels and mu-opioid receptor expression in adult primary sensory neurons.
The mu-opioid receptor agonists have a preferential effect on nociception in adults but their analgesic effect is less selective in neonates. Here we presented our finding that the mu-opioid receptor agonists had no effect on high voltage-activated Ca(2+) channels (HVACCs) in adult dorsal root ganglion (DRG) neurons that exhibited a prominent T-type Ca(2+) current. We also determined the mechanisms underlying the mu-opioid agonists' lack of effect on HVACCs in these neurons. The mu-opioid agonist [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enkephalin (DAMGO), morphine, and morphine 6-beta-D-glucuronide had no effect on either T-type or HVACC currents despite the presence of a large N-type Ca(2+) current in neurons with T-type Ca(2+) currents. DAMGO still had no effect on HVACC currents when T-type Ca(2+) channels were blocked in these neurons. However, intracellular dialysis of GTP-gamma-S to activate G proteins significantly attenuated HVACC currents. DRG neurons with T-type Ca(2+) currents showed little responses to capsaicin. Single-cell RT-PCR analysis revealed that the mu-opioid receptor mRNA was present only in adult DRG neurons lacking prominent T-type Ca(2+) currents. In the neonatal DRG, DAMGO inhibited HVACC currents in 31% neurons with T-type Ca(2+) currents. The mu-opioid receptor mRNA was detected in all neurons without T-type Ca(2+) currents and also in 28.6% of neurons with T-type Ca(2+) currents in the neonatal DRG. Our study provides novel information that adult DRG neurons with prominent T-type Ca(2+) currents do not express mu-opioid receptors. Expression of T-type Ca(2+) (Ca(V)3.2) channels and mu-opioid receptors may be developmentally co-regulated as some DRG neurons differentiate toward becoming nociceptive neurons.
Wu
Zi-Zhen
ZZ
Department of Anesthesiology and Perioperative Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Cai
You-Qing
YQ
Pan
Hui-Lin
HL
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001703:Biophysics; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D037102:Lectins / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D000701:Analgesics, Opioid; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D018755:GABA Agonists; D037102:Lectins; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D020866:omega-Conotoxin GVIA; D001418:Baclofen; D002211:Capsaicin