Atrial natriuretic peptide inhibits the phosphoinositide hydrolysis in murine Leydig tumor cells.
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.
Khurana
M L
ML
Department of Biochemistry & Molecular Biology, Medical College of Georgia, School of Medicine, Augusta 30912, USA.
Pandey
K N
KN
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006868:Hydrolysis; D007294:Inositol / Q000378:metabolism; D007984:Leydig Cell Tumor / Q000378:metabolism*; D008297:Male; D051379:Mice; D010716:Phosphatidylinositols / Q000378:metabolism*; D013736:Testicular Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D010716:Phosphatidylinositols; D001127:Arginine Vasopressin; C016276:8-bromocyclic GMP; D007294:Inositol; D009320:Atrial Natriuretic Factor; C041715:6-anilino-5,8-quinolinedione; D006162:Guanylate Cyclase; D006152:Cyclic GMP