Nitric-oxide-induced cGMP synthesis in cholinergic neurons in the rat brain.
Nitric oxide (NO)-mediated cGMP synthesis is localized throughout the rat brain in close proximity to the NO-synthase-containing structures. However, characterization of the cGMP synthesizing structures in terms of co-localization with the classical neurotransmitter systems has not yet been reported. Here we present evidence, using double immunostaining for cGMP and the vesicular acetylcholine transporter, that virtually all of the cholinergic fibers in the cerebral cortex and the majority of the cholinergic fibers in the basal ganglia accumulate cGMP in response to a NO donor. In these areas, only few cGMP-containing fibers were observed not to be part of the cholinergic system. Co-localization between cGMP and the vesicular acetylcholine transporter was only observed to a minor degree in the ventral forebrain, the hippocampus, the reticular thalamic nucleus, and the nucleus ambiguus. No association of cGMP synthesis with the cholinergic system was observed to a similar extent in other brain areas. These results, in combination with literature data on the distribution of cholinergic receptors in the rat brain, suggest that NO has an anterograde and/or retrograde signaling function on subsets of cholinergic neurons.
de Vente
J
J
European Graduate School of Neuroscience, Maastricht University, Department of Psychiatry and Neuropsychology, The Netherlands. j.devente@np.unimaas.nl
Markerink-van Ittersum
M
M
Axer
H
H
Steinbusch
H W
HW
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001479:Basal Ganglia / Q000166:cytology / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D002799:Cholinergic Fibers / Q000737:chemistry / Q000201:enzymology*; D006152:Cyclic GMP / Q000032:analysis / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008297:Male; D026901:Membrane Transport Proteins; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D000109:Acetylcholine