Nicotinic receptor alpha 7-subunits are coupled to the stimulation of nitric oxide synthase in rat dorsal root ganglion neurons.
In dorsal root ganglia (DRG) intraganglionic communication takes place both among neurons and between neurons and satellite cells. One diffusible substance involved in this signalling is nitric oxide (NO), and acetylcholine (ACh) is a candidate for the stimulation of intraganglionic NO synthesis. DRG neurons react to ACh-receptor stimulation with NO-dependent cGMP production. Here, we investigated the role of the alpha 7-subunit containing Ca(2+)-permeable nicotinic ACh receptors (nAChR) in this process. The alpha 7-nAChR mRNA and the protein were expressed in virtually all lumbar DRG neurons as evidenced by laser-assisted cell picking and oligo cell RT-PCR, in situ hybridisation and immunohistochemistry. Strong alpha 7-nAChR immunoreactivity was present in vanilloid receptor 1-immunoreactive, i.e. nociceptive, neurons. A neuronal production of NO in response to nicotine could be demonstrated in DRG slice preparations utilising the NO-sensitive fluorescent indicator diaminofluorescein diacetate (DAF-2DA). This stimulation of NO production was sensitive to inhibition of alpha 7-nAChR by mecamylamine and alpha-bungarotoxin, to inhibition of nitric oxide synthase (NOS) with L-NAME and L-NMMA, and to the blockade of voltage-operated Ca(2+) channels by verapamil. The results show the presence of the alpha 7-nAChR subunit in nociceptive rat DRG neurons and provide evidence for its coupling to NOS activation, indicating a role of this pathway in the intraganglionic communication in sensory ganglia.
Haberberger
Rainer Viktor
RV
Institute for Anatomy and Cell Biology, Justus-Liebig-University, Aulweg 123, 35385 Giessen, Germany. rainer.v.haberberger@anatomie.med.uni-giessen.de
Henrich
Michael
M
Lips
Katrin Susanne
KS
Kummer
Wolfgang
W
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002450:Cell Communication; D006152:Cyclic GMP / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism*; D008464:Mecamylamine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000737:chemistry; D009474:Neurons / Q000378:metabolism*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D050916:TRPV Cation Channels; D014700:Verapamil / Q000494:pharmacology; D064569:alpha7 Nicotinic Acetylcholine Receptor; D019323:omega-N-Methylarginine / Q000737:chemistry
D002038:Bungarotoxins; D015220:Calcium Channels; C579165:Chrna7 protein, rat; D018733:Nicotinic Antagonists; D011955:Receptors, Drug; D011978:Receptors, Nicotinic; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D064569:alpha7 Nicotinic Acetylcholine Receptor; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D008464:Mecamylamine; D014700:Verapamil; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester