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

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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 μM LY 83583 also inhibited the ANP-stimulated guanylyl cyclase activity and the intracellular accumulation of cGMP by more than 65–70%. The inhibition of eGMP-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.

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  1. Department of Biochemistry & Molecular Biology, Medical College of Georgia, School of Medicine, 30912, Augusta, Georgia, USA

    Madan L. Khurana & Kailash N. Pandey

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  1. Madan L. Khurana
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  2. Kailash N. Pandey
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Established Investigator of the American Heart Association

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Khurana, M.L., Pandey, K.N. Atrial natriuretic peptide inhibits the phosphoinositide hydrolysis in murine Leydig tumor cells. Mol Cell Biochem 158, 97–105 (1996). https://doi.org/10.1007/BF00225834

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  • DOI: https://doi.org/10.1007/BF00225834

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