Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glomeruli at the posterior margin of the main olfactory bulb differ in several respects from those located in the remainder of the bulb; e.g., the olfactory sensory neurons (OSNs) that project here exhibit a distinct biochemical phenotype and signal transduction pathway, the microcircuitry of the glomeruli is substantially altered, and the glomeruli are activated by unconventional odorants. In the present work, we report that the monoclonal antibodies 2C6 and MAb213 label distinct subsets of OSNs in the olfactory epithelium (OE), including their axons to their terminations in the main olfactory bulb (MOB). Neurons immunopositive with 2C6 are concentrated in the cul-de-sacs of ectoturbinates 1 and 2 and of endoturbinate IV. Unlike the vast majority of OSNs, 2C6(+) neurons express olfactory marker protein (OMP) at a low level, but their failure to stain with anti-GAP-43 labeling indicates that the OMP "weak" neurons are nonetheless mature. Glomeruli positive for 2C6 are bilaterally symmetrical and occupy reproducible positions along the posterior margin of the MOB. Three of these are very large, and we refer to them as the lateral, posterior ventral, and anterior ventral 2C6(+) necklace glomeruli. MAb213(+) neurons are concentrated in the posteriormost tips of the cul-de-sacs and recesses at the reflection of the OE at the cribriform plate. Like 2C6(+) neurons, MAb213(+) OSNs are weakly labeled with anti-OMP but are fully mature. MAb213(+) glomeruli are also bilaterally symmetrical; they occupy reproducible positions along the posterior margin of the MOB. The three largest glomeruli occupy lateral, posterior ventral, and posterior positions; the first two are found close to the aforementioned 2C6(+) glomeruli. MAb213 also intensely labels one of the glomeruli of the modified glomerular complex, a string of small glomeruli ventrally, and another string dorsal to the accessory olfactory bulb. Acetylcholinesterase (AChE) histochemical staining of adjacent sections showed that many, but not all, MAb213(+) glomeruli colocalize with dense or moderate AChE staining. Thus, it is likely that the "necklace olfactory glomeruli" (Shinoda et al., 1990, 1993) and the phosphodiesterase (PDE2)(+) glomeruli (Juilfs et al., 1997) are a subset(s) of the MAb213(+) glomeruli. On the other hand, 2C6(+) glomeruli are not associated with AChE staining. These data indicate that the 2C6(+) glomeruli comprise a novel subset in the posterior MOB. In addition to the 2C6(+) and MAb213(+) necklace glomeruli, there is another distinct set of glomeruli at the posterior margin of the bulb that are OMP(-), 2C6(-), and MAb213(-). In summary, the current work indicates that glomeruli at the posterior margin of the bulb, which are necklace glomeruli in terms of location and appearance, are actually heterogeneous and may subserve specialized functions within the olfactory system.
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PMID:Immunohistochemical identification of discrete subsets of rat olfactory neurons and the glomeruli that they innervate. 936 50

The olfactory cyclic nucleotide-gated channel subunit 1 (OCNC1) is required for signal transduction in olfactory receptor cells. To further investigate the role of this channel in the olfactory system, the biochemical and morphological consequences of targeted disruption of OCNC1 were investigated in adult mice. Null as compared to wild-type mice had smaller olfactory bulbs, suggesting compromised development of the central target of the receptor cells. Ectopic olfactory marker protein (OMP)-stained fibers localized to the external plexiform layer reflected the relative immaturity of the olfactory bulb in the null mice. The olfactory epithelium of the knock-out mouse was thinner and showed lower expression of olfactory marker protein and growth-associated protein 43, indicating decreases in both generation and maturation of receptor cells. Tyrosine hydroxylase (TH) expression in the olfactory bulb, examined as a reflection of afferent activity, was reduced in the majority of periglomerular neurons but retained in atypical or "necklace" glomeruli localized to posterior aspects of the olfactory bulb. Double label studies demonstrated that the remaining TH-immunostained neurons received their innervation from a subset of receptor cells previously shown to express a phosphodiesterase that differs from that found in most receptor cells. These data indicate that expression of OCNC1 is required for normal development of the olfactory epithelium and olfactory bulb. The robust expression of TH in some periglomerular cells in the OCNC1-null mice suggests that receptor cells innervating these glomeruli may use an alternate signal transduction pathway.
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PMID:Targeted deletion of a cyclic nucleotide-gated channel subunit (OCNC1): biochemical and morphological consequences in adult mice. 1053 36

We have recently shown that unilateral naris occlusion (UNO) causes an increase in olfactory marker protein (OMP) immunoreactivity (IR) in mouse olfactory sensory neurons (OSN) from the occluded side of the nasal cavity and a decrease in OMP-IR on the non-occluded side, relative to controls. Given OMP's demonstrated role in olfactory modulation, these OMP-IR changes have been interpreted as a compensatory response by OSNs to odor deprivation on the occluded side and to supernormal exposure to odor on the non-occluded side of the nasal cavity. In the current study, we examined the developmental timing and the regional distribution of this process throughout the nasal cavity using immunocytochemistry. Results demonstrate that OMP-IR diverges in OSNs from the occluded side relative to the non-occluded side of the nasal cavity within eleven days after UNO, with statistically significant differences measurable after 17 days (n=16). We also measured relative levels of the Type 4 phosphodiesterase (PDE4A), another potential olfactory modulator, in nasal cavity tissue from UNO (n=8) and untreated mice (n=9) using western blots and immunocytochemistry. Like OMP, PDE4A-IR increased on the occluded side of the nasal cavity after UNO. Finally, we used immunocytochemistry to assess relative levels of olfactory-specific adenylyl cyclase (ACIII, n=4) and G-protein (Golf, n=2) in OSNs from the occluded and non-occluded sides of the nasal cavity of UNO mice. Following UNO, ACIII but not Golf -IR levels diverged comparing the occluded to the non-occluded sides of the nasal cavity. Taken together, our findings provide support for the previously unknown phenomenon of compensatory responses by OSNs to odor environment.
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PMID:Naris occlusion alters transductory protein immunoreactivity in olfactory epithelium. 1649 79

The Grueneberg ganglion (GG) is a cluster of neurons localized to the vestibule of the anterior nasal cavity. Based on axonal projections to the olfactory bulb of the brain, as well as expression of olfactory receptors and the olfactory marker protein, it is considered a chemosensory subsystem. Recently, it was observed that in mice, GG neurons respond to cool ambient temperatures. In mammals, coolness-induced responses in highly specialized neuronal cells are supposed to rely on the ion channel TRPM8, whereas in thermosensory neurons of the nematode worm Caenorhabditis elegans, detection of environmental temperature is mainly mediated by cyclic guanosine monophosphate (cGMP) pathways, in which cGMP is generated by transmembrane guanylyl cyclases. To unravel the molecular mechanisms underlying coolness-induced responses in GG neurons, potential expression of TRPM8 in the murine GG was investigated; however, no evidence was found that this ion channel is present in the GG. By contrast, a substantial number of GG neurons was observed to express the transmembrane guanylyl cyclase subtype GC-G. In the nose, GC-G expression appears to be confined to the GG since it was not detectable in other nasal compartments. In the GG, coolness-stimulated responses are only observed in neurons characterized by the expression of the olfactory receptor V2r83. Interestingly, expression of GC-G in the GG was found in this V2r83-positive subpopulation but not in other GG neurons. In addition to GC-G, V2r83-positive GG cells also co-express the phosphodiesterase PDE2A. Thus, in summary, coolness-sensitive V2r83-expressing GG neurons are endowed with a cGMP cascade which might underlie thermosensitivity of these cells, similar to the cGMP pathway mediating thermosensation in neurons of C. elegans.
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PMID:Expression of cGMP signaling elements in the Grueneberg ganglion. 1883 Jun 17

The mammalian nose employs several olfactory subsystems to recognize and transduce diverse chemosensory stimuli. These subsystems differ in their anatomical position within the nasal cavity, their targets in the olfactory forebrain, and the transduction mechanisms they employ. Here we report that they can also differ in the strategies they use for stimulus coding. Necklace glomeruli are the sole main olfactory bulb (MOB) targets of an olfactory sensory neuron (OSN) subpopulation distinguished by its expression of the receptor guanylyl cyclase GC-D and the phosphodiesterase PDE2, and by its chemosensitivity to the natriuretic peptides uroguanylin and guanylin and the gas CO(2). In stark contrast to the homogeneous sensory innervation of canonical MOB glomeruli from OSNs expressing the same odorant receptor (OR), we find that each necklace glomerulus of the mouse receives heterogeneous innervation from at least two distinct sensory neuron populations: one expressing GC-D and PDE2, the other expressing olfactory marker protein. In the main olfactory system it is thought that odor identity is encoded by a combinatorial strategy and represented in the MOB by a pattern of glomerular activation. This combinatorial coding scheme requires functionally homogeneous sensory inputs to individual glomeruli by OSNs expressing the same OR and displaying uniform stimulus selectivity; thus, activity in each glomerulus reflects the stimulation of a single OSN type. The heterogeneous sensory innervation of individual necklace glomeruli by multiple, functionally distinct, OSN subtypes precludes a similar combinatorial coding strategy in this olfactory subsystem.
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PMID:Heterogeneous sensory innervation and extensive intrabulbar connections of olfactory necklace glomeruli. 1924 78

Voltage-gated calcium (Cav) channels are a prerequisite for signal transmission at the first olfactory sensory neuron (OSN) synapse within the glomeruli of the main olfactory bulb (MOB). We showed previously that the N-type Cav channel subunit Cav2.2 is present in the vast majority of glomeruli and plays a central role in presynaptic transmitter release. Here, we identify a distinct subset of glomeruli in the MOB of adult mice that is characterized by expression of the P/Q-type channel subunit Cav2.1. Immunolocalization shows that Cav2.1+ glomeruli reside predominantly in the medial and dorsal MOB, and in the vicinity of the necklace glomerular region close to the accessory olfactory bulb. Few glomeruli are detected on the ventral and lateral MOB. Cav2.1 labeling in glomeruli colocalizes with the presynaptic marker vGlut2 in the axon terminals of OSNs. Electron microscopy shows that Cav2.1+ presynaptic boutons establish characteristic asymmetrical synapses with the dendrites of second-order neurons in the glomerular neuropil. Cav2.1+ glomeruli receive axonal input from OSNs that express molecules of canonical OSNs: olfactory marker protein, the ion channel Cnga2, and the phosphodiesterase Pde4a. In the main olfactory epithelium, Cav2.1 labels a distinct subpopulation of OSNs whose distribution mirrors the topography of the MOB glomeruli, that shows the same molecular signature, and is already present at birth. Together, these experiments identify a unique Cav2.1+ multiglomerular domain in the MOB that may form a previously unrecognized olfactory subsystem distinct from other groups of necklace glomeruli that rely on cGMP signaling mechanisms.
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PMID:P/Q Type Calcium Channel Cav2.1 Defines a Unique Subset of Glomeruli in the Mouse Olfactory Bulb. 3023 29