Search results

1

Particulate guanylyl cyclases: multiple mechanisms of activation.

100%

Kobiałka M., Gorczyca W. A.

|

2000

|

vol. 47

|

issue 3

517-528

EN

Cyclic GMP (cGMP), a key messenger in several signal transduction pathways, is synthesized from GTP by a family of enzymes termed guanylyl cyclases, which are found in two forms: cytosolic (soluble) and membrane-bound (particulate). The past decade has brought significant progress in understanding the molecular mechanisms that underlie the regulation of particulate guanylyl cyclases and new members of their family have been identified. It has become more evident that the basic mechanism of catalysis of guanylyl cyclases is analogous to that recognized in adenylyl cyclases. Here we review the known basic mechanisms that contribute to the regulation of particulate guanylyl cyclases.

2

Hydrolysis of cyclic GMP in rat peritoneal macrophages.

100%

Witwicka H., Kobiałka M., Gorczyca W. A.

|

2002

|

vol. 49

|

issue 4

891-897

EN

Intact rat peritoneal macrophages (rPM) treated with 3-isobutyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterases (PDEs), accumulated more cGMP than untreated cells. A PDE activity toward [3H]cGMP was detected in the soluble and particulate fractions of rPM. The hydrolysis of cGMP was Ca2+/calmodulin-independent but increased in the presence of cGMP excess. Similar results were obtained when [3H]cAMP was used as a substrate. The hydrolytic activity towards both nucleotides was inhibited in the presence of IBMX. Therefore, the PDEs of families 2, 5, 10 and 11 are potential candidates for cGMP hydrolysis in the rPM. They may not only regulate the cGMP level in a feedback-controlled way but also link cGMP-dependent pathways with those regulated by cAMP.

3

Metabolism of cyclic GMP in peritoneal macrophages of rat and guinea pig.

63%

Kobiałka M., Witwicka H., Siednienko J., Gorczyca W. A.

|

2003

|

vol. 50

|

issue 3

837-847

EN

The aim of our studies was to establish which enzymes constitute the "cGMP pathway" in rat and guinea pig peritoneal macrophages (PM). We found that in guinea pig PM synthesis of the nucleotide was significantly enhanced in response to activators of soluble guanylyl cyclase (sGC) and it was only slightly stimulated by specific activators of particulate guanylyl cyclases (pGC). In contrast, rat PM responded strongly to atrial natriuretic peptide (ANP), the activator of pGC type A. The rat cells synthesized about three-fold more cGMP than an equal number of the guinea pig cells. The activity of phosphodiesterases (PDE) hydrolyzing cGMP was apparently regulated by cGMP itself in PM of both species and again it was higher in the rat cells than in those isolated from guinea pig. However, guinea pig PM revealed an activity of Ca2+/calmodulin-dependent PDE1, which was absent in the rat cells. Using Western blotting analysis we were unable to detect the presence of cGMP-dependent protein kinase 1 (PKG1) in PM isolated from either species. In summary, our findings indicate that particulate GC-A is the main active form of GC in the rat PM, while in guinea pig macrophages the sGC activity dominates. Since the profiles of the PDE activities in rat and guinea pig PM are also different, we conclude that the mechanisms regulating cGMP metabolism in PM are species-specific. Moreover, our results suggest that targets for cGMP other than PKG1 should be present in PM of both species.

Refine search results

3 Acta Biochimica Polonica

1 2003

1 2002

1 2000

3 Gorczyca W. A.

3 Kobiałka M.

2 Witwicka H.

1 Siednienko J.

Particulate guanylyl cyclases: multiple mechanisms of activation.

Hydrolysis of cyclic GMP in rat peritoneal macrophages.

Metabolism of cyclic GMP in peritoneal macrophages of rat and guinea pig.