ANP-mediated cGMP signaling and phosphodiesterase inhibition in the rat cervical spinal cord.
Natriuretic peptides (NP) and the corresponding receptors are present in the rodent spinal cord. We have studied the structures which respond to atrial natriuretic peptide, brain natriuretic peptide, or C-type natriuretic peptide with an increased synthesis of cGMP. NP-responsive cGMP-producing structures were observed in laminae I-III, and X, and in addition in ependymal cells, astrocytes and a subpopulation of dorsal root ganglion cells. As the cGMP concentration is controlled by the rate of synthesis and the rate of breakdown by phosphodiesterases, we studied NP-responsive structures in spinal cord slices incubated in the presence of different phosphodiesterase inhibitors. We studied EHNA and BAY 60-7550 as selective PDE2 inhibitors, sildenafil as a selective PDE5 inhibitors, dipyridamole as a mixed type PDE5 and PDE10 inhibitor, rolipram as a PDE4 inhibitor, and SCH 81566 as a selective PDE9 inhibitor. Double immunostainings showed that cGMP-IR colocalized partial with the vesicular acetylcholine transporter molecule in lamina X, with Substance P in a subpopulation of neuronal fibers situated dorsolateral, and with a subpopulation of CGRP-IR dorsal root ganglion neurons. Colocalization of cGMP-IR was absent with parvalbumin, synaptophysin, and the vesicular transporter molecules for GABA and glutamate. It is concluded that NPs in the spinal cord are probably involved in integrating intersegmental sensory processing in the spinal cord although the greater part of the NP-responsive cGMP-producing fibers could not be characterized. PDE2, 5, and 9 are involved in regulating NP-stimulated cGMP levels in the spinal cord. NPs may have a role in regulating cerebrospinal fluid homeostasis.
de Vente
J
J
European Graduate School of Neuroscience (EURON), Maastricht University, Department of Psychiatry and Neuropsychology, UNS50, POB 616, 6200 MD Maastricht, The Netherlands. j.devente@np.unimaas.nl
Markerink-van Ittersum
M
M
Vles
J S H
JS
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000378:metabolism* / Q000494:pharmacology; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002574:Cervical Vertebrae; D006152:Cyclic GMP / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004805:Ependyma / Q000187:drug effects / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000378:metabolism / Q000494:pharmacology; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism / Q000494:pharmacology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects / Q000378:metabolism*; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism
D004791:Enzyme Inhibitors; D020033:Protein Isoforms; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D013373:Substance P; D009320:Atrial Natriuretic Factor; D010727:Phosphoric Diester Hydrolases; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide