NO-mediated cGMP synthesis in cholinergic neurons in the rat forebrain: effects of lesioning dopaminergic or serotonergic pathways on nNOS and cGMP synthesis.
Nitric oxide synthase (NOS) activity and NO-mediated cGMP synthesis were studied in the rat forebrain of control animals and animals which had received a unilateral lesioning of dopaminergic or serotonergic pathways. Lesioning of the dopaminergic innervation using 6-hydroxydopamine resulted in a 50% decrease in NOS activity in the lesioned frontal cortex and caudate putamen. Lesioning of the serotonergic innervation using 5,7-dihydroxytryptamine had no effect on NOS activity. NO-mediated cGMP accumulation in rat forebrain slices was not affected by 6-hydroxydopamine or 5,7, -dihydroxytryptamine lesioning. Using cGMP immunocytochemistry, it was demonstrated that NO-mediated cGMP synthesis was absent from dopaminergic, serotonergic, GABA-ergic and neuronal NOS-containing nerve fibres. A minor colocalization of cGMP immunoreactivity was found in parvalbumin-containing fibres in the cortex. Extensive colocalization between cGMP immunoreactivity and the acetylcholine transporter was found in all cortical areas and in the caudate putamen. There was no effect of the lesions on this colocalization. These results demonstrate NO-mediated cGMP accumulation in cholinergic fibres in the forebrain of the rat and suggest an anterograde signalling function of NO in cholinergic neuronal systems in the cortex and caudate putamen of the rat.
de Vente
J
J
Maastricht University, Department of Psychiatry and Neuropsychology, POB 616, 6200 MD Maastricht, The Netherlands. j.devente@np.unimaas.nl
Markerink-van Ittersum
M
M
van Abeelen
J
J
Emson
P C
PC
Axer
H
H
Steinbusch
H W
HW
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015116:5,7-Dihydroxytryptamine / Q000633:toxicity; D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D002799:Cholinergic Fibers / Q000378:metabolism*; D006152:Cyclic GMP / Q000096:biosynthesis*; D004298:Dopamine / Q000502:physiology*; D004790:Enzyme Induction; D027342:Excitatory Amino Acid Transporter 2; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000032:analysis; D008297:Male; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052248:Nitric Oxide Synthase Type I; D016627:Oxidopamine / Q000633:toxicity; D010320:Parvalbumins / Q000032:analysis; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017981:Receptors, Neurotransmitter / Q000032:analysis; D012701:Serotonin / Q000502:physiology*; D013238:Stereotaxic Techniques; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D027342:Excitatory Amino Acid Transporter 2; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D017981:Receptors, Neurotransmitter; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; D015116:5,7-Dihydroxytryptamine; D009569:Nitric Oxide; D012701:Serotonin; D016627:Oxidopamine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; D006152:Cyclic GMP; D000109:Acetylcholine; D015056:1-Methyl-3-isobutylxanthine; D004298:Dopamine