Inhibitory action of α-human atrial natriuretic peptide on noradrenaline-induced synthesis of myo-inositol 1,4,5-trisphosphate in the smooth muscle cells of rabbit aorta

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Abstract
1 Interactions between the synthesis of myo-inositol 1,4,5-trisphosphate (IP3) and guanosine 3′:5′-cyclic monophosphate (cyclic GMP) in the smooth muscle cells of the rabbit aorta were investigated. 2 In the presence or absence of vascular endothelium, noradrenaline (NA; 5 μm) consistently reduced the amount of phosphatidylinositol 4,5-bisphosphate (PI-P2) and increased both phosphatidic acid (PA) and IP3. 3 In the presence or absence of endothelium, acetylcholine (ACh; 100 μm but not 5 μm) slightly increased the amount of IP3, but exposure to ACh (100 μm) 4 min after application of NA did not modify NA-induced synthesis of IP3. 4 ACh (100 μm) markedly enhanced the synthesis of cyclic GMP in the presence of endothelium but not in the endothelium-denuded tissues. 5 Prazosin (5 μm) but not dibutyryl cyclic GMP (db-cyclic GMP; 100 μm) blocked the hydrolysis of PI-P2 induced by 5 μm NA. Synthesis of IP3 induced by NA, as estimated with [3H]-inositol was not modified by application of 100 μm db-cyclic AMP or db-cyclic GMP. 6 α-Human atrial natriuretic peptide (α-hANP; 0.1 μm) increased cyclic GMP in the presence or absence of endothelium. α-hANP (0.1 μm) consistently inhibited the hydrolysis of PI-P2 induced by 5 μm NA. 7 The results indicate that synthesis of IP3 is inhibited neither by the synthesis of cyclic GMP in the cytosol nor by cyclic GMP itself. However, synthesis of IP3 through hydrolysis of PI-P2 may be inhibited by an interaction between some steps in the IP3 synthetic process and by the activation of the α-hANP-guanylate cyclase process at the sarcolemma.

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