Atrial natriuretic peptide inhibits the phosphoinositide hydrolysis in murine Leydig tumor cells.

Abstract

The ability of ANP to inhibit the hydrolysis of phosphoinositides was examined in [3H] myoinositol-labeled intact murine Leydig tumor (MA-10) cells. Arginine vasopressin (AVP) stimulated the formation of inositol monophosphate (IP1), inositol bisphosphate (IP2), and inositol trisphosphate (IP3) both in a time-and dose-dependent manner in MA-10 cells. ANP inhibited the AVP-induced formation of IP1, IP2, and IP3 in these cells. The inhibitory effect of ANP on the AVP-stimulated formation of IP1, IP2, and IP3 accounted for 30%, 38% and 42%, respectively, which was observed at the varying concentrations of AVP. ANP caused a dose-dependent attenuation in AVP-stimulated production of IP1, IP2 and IP3 with maximum inhibition at 100 nM concentration of ANP. The production of inositol phosphates was inhibited in the presence of 8-bromo cGMP in a dose-dependent manner, whereas dibutyryl-cAMP had no effect on the generation of these metabolites. The LY 83583, an inhibitor of guanylyl cyclase and cGMP production, abolished the inhibitory effect of ANP on the AVP-stimulated production of inositol phosphates. Furthermore, 10 microM LY 83583 also inhibited the ANP-stimulated guanylyl cyclase activity and the intracellular accumulation of cGMP by more than 65-70%. The inhibition of cGMP-dependent protein kinase by H-8, significantly restored the levels of AVP-stimulated inositol phosphates in the presence of either ANP or exogenous 8-bromo cGMP. The results of this study suggest that ANP exerts an inhibitory effect on the production of inositol phosphates in murine Leydig tumor (MA-10) cells by mechanisms involving cGMP and cGMP-dependent protein kinase.

• Authors: M L Khurana, K N Pandey
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 158 Issue 2 Pg. 97-105 (May 24 1996) ISSN: 0300-8177 [Print] Netherlands
• PMID: 8817470 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Aminoquinolines
• Enzyme Inhibitors
• Phosphatidylinositols
• Arginine Vasopressin
• 8-bromocyclic GMP
• Inositol
• Atrial Natriuretic Factor
• 6-anilino-5,8-quinolinedione
• Guanylate Cyclase
• Cyclic GMP

Topics

• Aminoquinolines (pharmacology)
• Animals
• Arginine Vasopressin (pharmacology)
• Atrial Natriuretic Factor (pharmacology)
• Cyclic GMP (analogs & derivatives, metabolism, pharmacology)
• Enzyme Inhibitors (pharmacology)
• Guanylate Cyclase (antagonists & inhibitors)
• Hydrolysis
• Inositol (metabolism)
• Leydig Cell Tumor (metabolism)
• Male
• Mice
• Phosphatidylinositols (metabolism)
• Testicular Neoplasms (metabolism)
• Tumor Cells, Cultured (metabolism)