Abstract
Opioids have a selective effect on nociception with little effect on other sensory modalities. However, the cellular mechanisms for this preferential effect are not fully known. Two broad classes of nociceptors can be distinguished based on their growth factor requirements and binding to isolectin B4(IB4). In this study, we determined the difference in the modulation of voltage-gated Ca2+ currents by [d-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO, a specific μ opioid agonist) between IB4-positive and -negative small dorsal root ganglion (DRG) neurons. Whole-cell voltage-clamp recordings were performed in acutely isolated DRG neurons in adult rats. Both 1–10 μM DAMGO and 1 to 10 μM morphine had a greater effect on high voltage-activated Ca2+ currents in IB4-negative than IB4-positive cells. However, DAMGO had no significant effect on T-type Ca2+ currents in both groups. The N-type Ca2+ current was the major subtype of Ca2+ currents inhibited by DAMGO in both IB4-positive and -negative neurons. Although DAMGO had no effect on L-type and R-type Ca2+ currents in both groups, it produced a larger inhibition on N-type and P/Q-type Ca2+ currents in IB4-negative than IB4-positive neurons. Furthermore, double labeling revealed that there was a significantly higher μ opioid receptor immunoreactivity in IB4-negative than IB4-positive cells. Thus, these data suggest that N-and P/Q-type Ca2+ currents are more sensitive to inhibition by the μ opioids in IB4-negative than IB4-positive DRG neurons. The differential sensitivity of voltage-gated Ca2+ channels to the μ opioids in subsets of DRG neurons may constitute an important analgesic mechanism of μ opioids.
Footnotes
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This study was supported by the National Institutes of Health Grants GM64830 and NS45602. H.L. Pan was a recipient of an Independent Scientist Career Award supported by the National Institutes of Health during the course of this study.
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doi:10.1124/jpet.104.073429.
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ABBREVIATIONS: DRG, dorsal root ganglion; NGF, nerve growth factor; IB4, Griffonia simplicifolia isolectin B4; GDNF, glial cell line-derived neurotrophic factor; DMEM, Dulbecco's modified Eagle's medium; DAMGO, [d-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin; CTOP, d-Phe-Cys-Thr-d-Trp-Orn-Thr-Pen-Thr-NH2.
- Received June 28, 2004.
- Accepted July 27, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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