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

The localization of the particulate and soluble guanylate cyclase in the rat brain was studied using cGMP-immunocytochemistry. The cGMP was fixed to tissue protein using a formaldehyde fixative, and an antibody against cGMP was used which was raised against a cGMP-formaldehyde-thyroglobulin conjugate. We used the atrial natriuretic factor (ANF) as a model compound to stimulate the particulate enzyme and sodium nitroprusside (SNP) to stimulate the soluble enzyme. Sequential immunostaining for cGMP and glial fibrillary acidic protein (GFAP) showed that the great majority of the ANF-responsive, cGMP-producing cells were astrocytes. These ANF-responsive cells were found in discrete parts of the CNS; not all astrocytes in these regions were responsive to ANF. SNP stimulated cGMP in abundantly present neuronal fibres throughout the CNS; few neuronal cell bodies showed increased cGMP production after SNP. Moreover, SNP also raised cGMP in astrocytes, however, not all astrocytes showed the response to SNP. These results suggest that cells might be present in the CNS which contain both the soluble and the particulate guanylate cyclase. It was demonstrated that in the immature cerebellum, the cGMP was raised in glial structures in response to N-methyl-D-aspartate (NMDA), ANF, SNP, and kainic acid. The response to NMDA and kainic acid was sensitive to inhibition of the nitric oxide synthesis from L-arginine by NG-methyl-L-arginine. Surprisingly the response to ANF localized in the molecular layer and the granular layer was also sensitive to inhibition by NG-methyl-L-arginine, whereas the response to ANF in the deep nuclei was not. A small depolarization induced by 10 to 20 mmol/l K+ induced an increase in cGMP in chopped hippocampus tissue which showed a biphasic temporal characteristic. The initial, fast (30 sec), peak was shown to be localized in varicose fibres throughout the hippocampus, whereas the slower response (10 min) was localized in astrocytes. These studies demonstrate that the different enzymes which synthesize cGMP are differently localized. However, there is also a time dependency in the activation of the guanylate cyclases, which becomes apparent in different structures at different times. The possible role of cGMP as a regulator of ion homeostase is discussed.
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PMID:On the stimulation of soluble and particulate guanylate cyclase in the rat brain and the involvement of nitric oxide as studied by cGMP immunocytochemistry. 134 85

We have previously identified specific atriopeptin (ANP) receptors in cultured human thyroid cells and demonstrated that ANP reduced thyroglobulin (Tg) secretion. In this report the relationship of Tg inhibition to cyclic nucleotide intermediate pathways was explored, and the thyroidal ANP receptor was characterized by affinity cross-linking. Concentrations of Tg, cGMP, and cAMP were measured in medium from thyroid cells cocultured with ANP. ANP significantly inhibited cAMP production at the lower concentration of 0.1 nmol/L and stimulated cGMP levels at a higher concentration of 10 nmol/L. The percentage of inhibition of Tg release over the ANP range of 0.01-10 nmol/L appeared to parallel cAMP, but not cGMP, levels, suggesting that ANP acts via a cAMP pathway in the thyroid. Affinity cross-linking studies characterizing the ANP receptor in thyrocytes and a bovine endothelial cell line known to be cGMP responsive to ANP indicated a single unit ANP receptor of 140 kD coupled to guanylate cyclase in endothelial cells, while a 70-kD receptor was found in thyroid cells which specifically binds to ANP, atriopeptin-I, and atriopeptin-III. These studies in thyrocytes suggest that reduced Tg release may be mediated by a specific single 70-kD ANP receptor associated with an inhibitor cAMP pathway and provide additional insight into the nature of a newly described thyroid-ANP interaction.
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PMID:Characterization by affinity cross-linking of a receptor for atrial natriuretic peptide in cultured human thyroid cells associated with reductions in both adenosine 3',5'-monophosphate production and thyroglobulin secretion. 215 96

Thyrotropin (TSH) regulation of atrial natriuretic factor (ANF) receptors was studied in the rat thyroid follicular cell line, FRTL-5. Exposure of FRTL-5 cells to 1 mU/ml TSH for 7 days resulted in a tenfold increase in ANF receptors (Bmax = 188 fmol/mg protein) compared with control (Bmax = 18 fmol/mg protein), without affecting binding affinity. An identical treatment of porcine thyrocytes with TSH resulted in a 50% decrease in ANF binding sites. Displacement binding studies indicated that > 80% of the ANF receptors in FRTL-5 cells belong to the ANF-R1 (guanylate cyclase-coupled) receptor subtype. By contrast, > 98% of the ANF receptors in porcine thyrocytes were of the ANF-R2, or clearance, receptor subtype. Intracellular cGMP content was increased thirty-sixfold in FRTL-5 cells by 1 microM ANF, but only 2.5-fold in porcine thyrocytes. cAMP levels were unaffected by ANF in either cell type. Northern blot analysis of poly A mRNA extracted from FRTL-5 cells incubated 2 days in the presence of 100 nM ANF indicated a twofold increase in thyroglobulin mRNA content compared with control. These findings suggest that the ANF-R1 receptor, preferentially expressed in FRTL-5 cells and regulated by TSH, might play a role in regulating thyroid hormone production.
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PMID:Atrial natriuretic factor (ANF) binds to thyrotropin-regulated receptors in FRTL-5 cells and increases thyroglobulin mRNA. 793 23