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| CYCLIC 3',5'-NUCLEOTIDE DIESTERASES IN DYNAMICS OF CAMP AND CGMP IN RAT COLLECTING DUCT CELLS |
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| Author(s): YAMAKI M, MCINTYRE S, RASSIER ME, SCHWARTZ JH, DOUSA TP |
| Source: AMERICAN JOURNAL OF PHYSIOLOGY Volume: 262 Issue: 6 Pages: F957-F964 Part: Part 2 Published: JUN 1992 |
| Times Cited: 18 References: 33 |
| Abstract: We studied cyclic 3',5'-nucleotide phosphodiesterase (PDE) isozymes and their role in adenosine 3',5'-cyclic monophosphate (cAMP) and cGMP metabolism in a rat inner medullary collecting duct (IMCD) cell line. The homogenized and fractionated IMCD cells of cAMP-PDE and all of cGMP-PDE activity were found in the cytosol. The majority of cytosolic cAMP-PDE (> 50%) was isozyme PDE-IV; the Ca2+-calmodulin-sensitive PDE-I was present only in cytosol. Preincubation of IMCD cells with PDE-IV inhibitor rolipram markedly (5x) enhanced levels of cAMP both basal and in the presence of [Arg8]vasopressin (AVP). Cilostamide (for PDE-III) or vinpocetine had no effect, whereas PDE-I inhibitor 8-methoxymethyl-3-isobutyl-1-methylxanthine (8-MeoM-IBMX) enhanced AVP-dependent cAMP levels. Exposure of IMCD cells to 2-mu-M ionomycin decreased both basal and AVP-stimulated cAMP. Depletion of Ca2+ by preincubation of IMCD cells in the Ca2+-free medium with ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid markedly enhanced the stimulatory response of cAMP to AVP, and addition of 8-MeoM-IBMX further enhanced the AVP response. The levels of cGMP, basal or in response to atriopeptin (ANP), were not affected by PDE-V inhibitor zaprinast, but both inhibitors of PDE-I, 8-MeoM-IBMX and vinpocetine, increased basal cGMP, and 8-MeoM-IBMX also increased cGMP levels enhanced by ANP. The depletion of Ca2+ from IMCD cells alone had no effect on cGMP levels, but effects of 8-MeoM-IBMX and vinpocetine on the ANP-stimulated cGMP levels were enhanced. Our observations suggest that the overall cAMP turnover in IMCD cells is catalyzed by PDE-IV. Cytosolic PDE-I metabolizes the cAMP pool generated in response to AVP and may thereby serve as negative-feedback mechanism. Finally, the cGMP breakdown is catalyzed by cytosolic PDE-I. |
| Document Type: Article |
| Language: English |
Addresses:
1. MAYO CLIN & MAYO FDN, DIV NEPHROL, NEPHROL RES UNIT, 200 1ST ST, ROCHESTER, MN 55905 USA
2. MAYO CLIN & MAYO FDN, DEPT PHYSIOL & BIOPHYS, ROCHESTER, MN 55905 USA
3. BOSTON UNIV, BOSTON CITY HOSP, SCH MED, DEPT MED, RENAL SECT, BOSTON, MA 02118 USA
4. BOSTON UNIV, BOSTON CITY HOSP, SCH MED, THORNDIKE MEM LAB, BOSTON, MA 02118 USA |
| Publisher: AMER PHYSIOLOGICAL SOC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Physiology |
| IDS Number: JC377 |
| ISSN: 0002-9513 |
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