期刊
NEUROSCIENCE
卷 118, 期 4, 页码 941-948出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0306-4522(02)00915-6
关键词
estrogen; VGCCs; primary sensory neurons; nociception
资金
- NIDA NIH HHS [DA 13185] Funding Source: Medline
- NIDDK NIH HHS [DK 58173] Funding Source: Medline
- NINDS NIH HHS [NS 39495] Funding Source: Medline
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK058173] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS039495] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA013185] Funding Source: NIH RePORTER
Estrogen has been implicated in modulation of pain processing. Although this modulation occurs within the CNS, estrogen may also act on primary afferent neurons whose cell bodies are located within the dorsal root ganglia (DRG). Primary cultures of rat DRG neurons were loaded with Fura-2 and tested for ATP-induced changes in intracellular calcium concentration ([Ca2+](i)) by fluorescent ratio imaging. ATP, an algesic agent, induces [Ca2+](i) changes via activation of purinergic 2X (P2X) type receptors and voltage-gated Ca2+ channels (VGCC). ATP (10 muM) caused increased [Ca2+](i) transients (226.6.+/-16.7 nM, n = 42) in 53% of small to medium DRG neurons. A 5-min incubation with 17beta-estradiol (100 nM) inhibited ATP-induced [Ca2+](i) (164+/-14.6 nM, P<0.05) in 85% of the ATP-responsive DRG neurons, whereas the inactive isomer 17alpha-estradiol had no effect. Both the mixed agonist/ antagonist tamoxifen (1 muM) and specific estrogen receptor antagonist ICI 182780 (1 muM) blocked the estradiol inhibition of ATP-induced [Ca2+](i) transients. Estradiol coupled to bovine serum albumin, which does not diffuse through the plasma membrane, blocked ATP-induced [Ca2+](i), suggesting that estradiol acts at a membrane-associated estrogen receptor. Attenuation of [Ca2+](i) transients was mediated by estrogen action on VGCC. Nifedipine (10 muM), an L-type VGCC antagonist mimicked the effect of estrogen and when co-administered did not increase the estradiol inhibition of ATP-induced [Ca2+](i) transients. N- and P-type VGCC antagonists to omega-conotoxin GVIA (1 muM) and omega-agatoxin IVA (100 nM), attenuated the ATP-induced [Ca2+](i) transients. Co-administration of these blockers with estrogen induced a further decrease of the ATP-induced [Ca2+](i) flux. Together, these results suggest that although ATP stimulation of P2X receptors activates L-, N-, and P-type VGCC, estradiol primarily blocks L-type VGCC. The estradiol regulation of this ATP-induced [Ca2+](i) transients suggests a mechanism through which estradiol may modulate nociceptive signaling in the peripheral nervous system. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.
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