Mapping of neural nitric oxide synthase in the rat suggests frequent co-localization with NADPH diaphorase but not with soluble guanylyl cyclase, and novel paraneural functions for nitrinergic signal transduction.
Nitric oxide synthases (NOS Types I-III) generate nitric oxide (NO), which in turn activates soluble guanylyl cyclase (GC-S). The distribution of this NO-mediated (nitrinergic) signal transduction pathway in the body is unclear. A polyclonal monospecific antibody to rat cerebellum NOS-I and a monoclonal antibody to rat lung GC-S were employed to localize the protein components of this pathway in different rat organs and tissues. We confirmed the localization of NOS-I in neurons of the central and peripheral nervous system, where NO may regulate cerebral blood flow and mediate long-term potentiation. GC-S was located in NOS-negative neurons, indicating that NO acts as an intercellular signal molecule or neurotransmitter. However, NOS-I was not confined to neurons but was widely distributed over several non-neural cell types and tissues. These included glia cells, macula densa of kidney, epithelial cells of lung, uterus, and stomach, and islets of Langerhans. Our findings suggest that NOS-I is the most widely distributed isoform of NOS and, in addition to its neural functions, regulates secretion and non-vascular smooth muscle function. With the exception of bone tissue, NADPH-diaphorase (NADPH-d) activity was generally co-localized with NOS-I immunoreactivity in both neural and non-neural cells, and is a suitable histochemical marker for NOS-I but not a selective neuronal marker.
Schmidt
H H
HH
Northwestern University Medical School, Department of Pharmacology, Chicago, Illinois 60611.
Gagne
G D
GD
Nakane
M
M
Pollock
J S
JS
Miller
M F
MF
Murad
F
F
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002531:Cerebellum / Q000033:anatomy & histology / Q000201:enzymology*; D004797:Enzyme-Linked Immunosorbent Assay; D006162:Guanylate Cyclase / Q000378:metabolism*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase; D011233:Precipitin Tests; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction; D014018:Tissue Distribution
D007527:Isoenzymes; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase; D006162:Guanylate Cyclase