Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Soluble guanylyl cyclase is a heterodimeric (alpha, beta) enzyme generating the second messenger, cGMP, upon activation by the gaseous messenger, nitric oxide. The occurrence and distribution of alpha 1-, alpha 2-, beta 1- and beta 2-subunits were investigated in trigeminal and dorsal root ganglia on the mRNA and the protein level. Reverse transcription PCR analysis demonstrated mRNA coding for alpha 1-, alpha 2-, and beta 1-subunits in guinea-pig trigeminal and dorsal root ganglia. In agreement with these data, immunoreactivity to the alpha 1-subunit was found in satellite and Schwann cells, while alpha 2-subunit immunoreactivity was localized to axons of large diameter. The distribution of the beta 1-subunit could not be studied on the protein level since the antiserum was ineffective in immunohistochemistry. However, previous studies and the RT-PCR data argue in favour of alpha 1/beta 1-and alpha 2/beta 1-heterodimerization and colocalization. In both species, beta 2-subunit immunoreactivity was confined to neuronal perikarya, primarily of large diameter. Although these results were obtained with two different antibodies directed against different epitopes, the corresponding mRNA could not be detected by RT-PCR analysis. The reason for this discrepancy remains unclear, at present, but could be explained by a variant beta 2- or highly homologous as yet unidentified beta-subunit. This study demonstrates the presence of soluble guanylyl cyclase in sensory ganglia with a differential, cell type-specific distribution of the individual subunits.
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PMID:Subunits of soluble guanylyl cyclase in rat and guinea-pig sensory ganglia. 879

We investigated the mechanisms of endogenous nitric oxide (NO) modulation of lung sodium (Na(+)) transport. C57BL/6 mice injected intraperitoneally with the specific inducible NO synthase (iNOS) inhibitor 1400W (10 mg/kg every 8 h for 72 h) exhibited decreased alveolar nitrite levels and Na(+)-dependent amiloride-sensitive alveolar fluid clearance as compared with mice injected with vehicle. Similarly, pretreatment of mouse tracheal epithelial cells with 1400W abolished the inhibitory effects of amiloride on their Na(+) short circuit currents. On the other hand, mouse tracheal epithelial cells pretreated with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a specific inhibitor of guanylate cyclase, had lower levels of cGMP, but normal values of amiloride-sensitive Na(+) currents. Amiloride also inhibited whole-cell Na(+) currents across A549 cells treated with vehicle (K(i) = 249 nM), but had no effect in A549 cells treated with 1400W. Western blotting studies showed significantly lower levels of alpha and gammaENaC in lung tissues and alveolar type II (ATII) cells from iNOS(-/-) as well as iNOS(+/+) mice treated with 1400W, as compared with the corresponding values from vehicle-treated iNOS(+/+) mice. Similar values for ratios of alpha, beta, and gammaenac to gapdh were obtained by real-time polymerase chain reaction for iNOS(+/+) mice and iNOS(-/-) mice. We concluded that NO derived from iNOS under basal conditions is necessary for amiloride-sensitive Na(+) transport across lung epithelial cells and modulates the amount of alpha and gammaENaC via post-transcriptional, cGMP-independent mechanisms.
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PMID:Regulation of amiloride-sensitive Na(+) transport by basal nitric oxide. 1460 16