Properties and subcellular distribution of guanylate cyclase activity in rat renal medulla: correlation with tissue content of guanosine 3',5'-monophosphate.

The properties of the guanylate cyclase systems of outer and inner medulla of rat kidney were examined and compared with those of the renal cortex. A gradation in steady-state cyclic guanosine 3',5'-monophosphate (cGMP) levels was observed in incubated slices of these tissues (inner medula greater than outer medulla greater than cortex). This correlated with the proportion of total guanyl cyclase activity in the 100 000 g particulate fraction of each tissue, but was discordant with the relative activities of guanylate cyclase (highest in cortex) and of cGMP-phosphodiesterase (lowest in cortex) in whole tissue homogenates. Soluble guanylate cyclase of cortex and inner medulla exhibited typical Michaelis-Menten kinetics with an apparent Km for MnGTP of 0.11 mM, while the particulate enzyme from inner medulla exhibited apparent positive cooperative behavior and a decreased dependence on Mn2+. Thus, the particulate enzyme could play a key role in regulating cGMP levels inthe intact cell where Mn2+ concentrations are low. The soluble and particulate enzymes from inner medulla were further distinguished by their responses to several test agents. The soluble enzyme was activated by Ca2+, NaN3, NaNo2 and phenylhydrazine, whereas particulate activity was inhibited by Ca2+ and was unresponsive to the latter agents. In the presence of NaNo2, Mn2+ requirement of the soluble enzyme was reduced and equivalent to that of the particulate preparation. Moreover, relative responsiveness of the sollble enzyme to NaNO2 was potentiated when Mg2+ replaced Mn2+ as the sole divalent cation. These changes in metal requirements may be involved in the action of NaNO2 to increase cGMP in intact kidney. Soluble guanylate cyclase of cortex was clearly more responsive to stimulation by NaN3, Nano2, and phenylhydrazine that was soluble activity from either medullary tissue. The effectiveness of the agonists on soluble activity from outer and inner medulla cound also be distinguished. Accordingly, regulation and properties of soluble guanylate cyclase, as well as subcellular enzyme distribution, and distinct in the three regions of the kidney.

[1]  F. DeRubertis,et al.  Calcium-independent modulation of cyclic GMP and activation of guanylate cyclase by nitrosamines. , 1976, Science.

[2]  F. DeRubertis,et al.  Properties of the guanylate cyclase-guanosine 3':5'-monophosphate system of rat renal cortex. Activation of guanylate cyclase and calcium-independent modulation of tissue guanosine 3':5'-monophosphate by sodium azide. , 1976, The Journal of biological chemistry.

[3]  F. DeRubertis,et al.  Chromatographic separation of cyclic guanosine 3',5'-monophosphate from guanylate cyclase reaction mixtures. , 1976, Analytical biochemistry.

[4]  F. DeRubertis,et al.  The content and metabolism of cyclic adenosine 3', 5'-monophosphate and cyclic guanosine 3', 5'-monophosphate in adenocarcinoma of the human colon. , 1976, The Journal of clinical investigation.

[5]  G. Drummond,et al.  Guanylate cyclase of sea urchin sperm: subcellular localization. , 1976, Archives of biochemistry and biophysics.

[6]  J. Hardman,et al.  Enzymes of cyclic nucleotide metabolism in invertebrate and vertebrate sperm. , 1976, Archives of biochemistry and biophysics.

[7]  F. Murad,et al.  Activation of guanylate cyclase from rat liver and other tissues by sodium azide. , 1975, The Journal of biological chemistry.

[8]  F. Murad,et al.  Increases in cyclic GMP levels in brain and liver with sodium azide an activator of guanylate cyclase , 1975, Nature.

[9]  E. Neer,et al.  Guanylate cyclase from the rat renal medulla. Physical properties and comparison with adenylate cyclase. , 1975, The Journal of biological chemistry.

[10]  F. Murad,et al.  Localization of particulate guanylate cyclase in plasma membranes and microsomes of rat liver. , 1975, The Journal of biological chemistry.

[11]  F. Murad,et al.  Increased particulate and decreased soluble guanylate cyclase activity in regenerating liver, fetal liver, and hepatoma. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[12]  F. Murad,et al.  Two forms of guanylate cyclase in mammalian tissues and possible mechanisms for their regulation. , 1975, Metabolism: clinical and experimental.

[13]  G. Drummond,et al.  A modified assay of 3':5'-cyclic-AMP phosphodiesterase. , 1975, Analytical biochemistry.

[14]  T. Chrisman,et al.  Characterization of particulate and soluble guanylate cyclases from rat lung. , 1975, The Journal of biological chemistry.

[15]  D. Garbers,et al.  Effects of cations on guanylate cyclase of sea urchin sperm. , 1975, The Journal of biological chemistry.

[16]  F. Murad,et al.  Evidence for two different forms of guanylate cyclase in rat heart. , 1974, The Journal of biological chemistry.

[17]  W. Looney,et al.  Adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate: concentrations in Morris hepatomas of different growth rates. , 1973, Biochimica et biophysica acta.

[18]  A. Steiner,et al.  Effects of acidosis and alkalosis on 3',5'-GMP and 3',5'-AMP in renal cortex. , 1972, The American journal of physiology.

[19]  G. A. Thompson,et al.  Membrane formation in Tetrahymena pyriformis. 4. Lipid composition and biochemical properties of Tetrahymena pyriformis membrane systems , 1971 .

[20]  Thompson Wj,et al.  Multiple cyclic nucleotide phosphodiesterase activities from rat brain , 1971 .

[21]  E. Böhme.  [Guanyl cyclase. Biosynthesis of guanosine-3',5'-monophosphate in kidney and other rat tissues]. , 1970, European journal of biochemistry.

[22]  F. Epstein,et al.  METABOLISM OF THE RENAL MEDULLA. , 1965, The American journal of physiology.

[23]  A. Aperia,et al.  IMPLICATIONS OF URINE PO2 FOR RENAL MEDULLARY BLOOD FLOW. , 1964, The American journal of physiology.

[24]  P. H. Adams,et al.  Oxygen consumption and respiratory pigments of mitochondria of the inner medulla of the dog kidney. , 1962, Biochimica et biophysica acta.

[25]  G. Cahill,et al.  Metabolism of C14-labeled substrates by rabbit kidney cortex and medulla. , 1962, The American journal of physiology.

[26]  P. H. Adams,et al.  Energy metabolism of the renal medulla. , 1961, Biochimica et biophysica acta.

[27]  J. Pappenheimer,et al.  Oxygen pressure in urine and its relation to intrarenal blood flow. , 1958, The American journal of physiology.

[28]  J. Rhodin.  Electron microscopy of the kidney. , 1958, The American journal of medicine.

[29]  E. Farber,et al.  HISTOCHEMICAL LOCALIZATION OF SPECIFIC OXIDATIVE ENZYMES: II. LOCALIZATION OF DIPHOSPHOPYRIDINE NUCLEOTIDE AND TRIPHOSPHOPYRIDINE NUCLEOTIDE DIAPHORASES AND THE SUCCINDEHYDROGENASE SYSTEM IN THE KIDNEY , 1956, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[30]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.