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)

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

Sodium nitroprusside (SNP) spontaneously produces nitric oxide (NO). In many cell types, this activates the soluble form of the enzyme guanylyl cyclase (GC), resulting in the elevation of cGMP. We herein report the role of NO and cGMP on iodide uptake in primary cultures of calf thyroid cells. Iodide uptake is the limiting step in thyroid hormone biosynthesis and a typical functional parameter. The effect of SNP on this parameter was thus determined. In cells treated with TSH for 72 h, addition of 5 mM SNP for the last 2 h caused a significant inhibition on iodide uptake, with no change in cells not treated with TSH. This action was mimicked by an analogue of cGMP, 8Br-cGMP, and blocked by reduced hemoglobin, thus suggesting that it is mediated by the GC-cGMP pathway. SNP also inhibited the stimulation caused by forskolin or analogues of cAMP, indicating that the effect takes place in this pathway, which would be distal to cAMP generation. The accumulation of radioiodine by thyroid cells is a consequence of the balance between influx and efflux. The studies demonstrate that SNP does not affect iodide efflux, thus revealing that it inhibits the influx.
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PMID:Role of cyclic 3'5' guanosine monophosphate and nitric oxide in the regulation of iodide uptake in calf thyroid cells. 948 90

Orally administered small molecule agonists of soluble guanylate cyclase (sGC) induced increased numbers of osteoclasts, multifocal bone resorption, increased porosity, and new bone formation in the appendicular and axial skeleton of Sprague-Dawley rats. Similar histopathological bone changes were observed in both young (7- to 9-week-old) and aged (42- to 46-week-old) rats when dosed by oral gavage with 3 different heme-dependent sGC agonist (sGCa) compounds or 1 structurally distinct heme-independent sGCa compound. In a 7-day time course study in 7- to 9-week-old rats, bone changes were observed as early as 2 to 3 days following once daily compound administration. Bone changes were mostly reversed following a 14-day recovery period, with complete reversal after 35 days. The mechanism responsible for the bone changes was investigated in the thyroparathyroidectomized rat model that creates a low state of bone modeling and remodeling due to deprivation of thyroid hormone, calcitonin (CT), and parathyroid hormone (PTH). The sGCa compounds tested increased both bone resorption and formation, thereby increasing bone remodeling independent of calciotropic hormones PTH and CT. Based on these studies, we conclude that the bone changes in rats were likely caused by increased sGC activity.
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PMID:Oral administration of soluble guanylate cyclase agonists to rats results in osteoclastic bone resorption and remodeling with new bone formation in the appendicular and axial skeleton. 2514 29