期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 36, 页码 14507-14512出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0704965104
关键词
cGMP; natriuretic peptide; transduction; Gucy2d; CNGA3
资金
- NIDCD NIH HHS [R01 DC008295, R01 DC003773, R03DC04779, R01DC04553, R01 DC005633, R01DC00563, R01DC008295, R01 DC004553, R01 DC005249, R01DC05249, R01DC003773] Funding Source: Medline
- NIGMS NIH HHS [T32GM008181, T32 GM008181] Funding Source: Medline
The mammalian main olfactory epithelium (MOE) recognizes and transduces olfactory cues through a G protein-coupled, cAMP-dependent signaling cascade. Additional chemosensory transduction mechanisms have been suggested but remain controversial. We show that a subset of MOE neurons expressing the orphan receptor guanylyl cyclase GC-D and the cyclic nucleotide-gated channel subunit CNGA3 employ an excitatory cGMP-dependent transduction mechanism for chemodetection. By combining gene targeting of Gucy2d, which encodes GC-D, with patch clamp recording and confocal Ca2+ imaging from single dendritic knobs in situ, we find that GC-D cells recognize the peptide hormones uroguanylin and guanylin as well as natural urine stimuli. These molecules stimulate an excitatory, cGMP-dependent signaling cascade that increases intracellular Ca2+ and action potential firing. Responses are eliminated in both Gucy2d- and Cnga3-null mice, demonstrating the essential role of GC-D and CNGA3 in the transduction of these molecules. The sensitive and selective detection of two important natriuretic peptides by the GC-D neurons suggests the possibility that these cells contribute to the maintenance of salt and water homeostasis or the detection of cues related to hunger, satiety, or thirst.
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