Premium
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
Author(s) -
Kajikuri Junko,
Kuriyama Hirosi
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12964.x
Subject(s) - inositol , medicine , endocrinology , chemistry , acetylcholine , vascular smooth muscle , cyclic guanosine monophosphate , atrial natriuretic peptide , guanosine , phosphatidylinositol , second messenger system , cyclic gmp , endothelium , biochemistry , biology , signal transduction , smooth muscle , receptor , enzyme , nitric oxide
1 Interactions between the synthesis of myo‐inositol 1,4,5‐trisphosphate (IP 3 ) 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 μ m ) consistently reduced the amount of phosphatidylinositol 4,5‐bisphosphate (PI‐P 2 ) and increased both phosphatidic acid (PA) and IP 3 . 3 In the presence or absence of endothelium, acetylcholine (ACh; 100 μ m but not 5 μ m ) slightly increased the amount of IP 3 , but exposure to ACh (100 μ m ) 4 min after application of NA did not modify NA‐induced synthesis of IP 3 . 4 ACh (100 μ m ) markedly enhanced the synthesis of cyclic GMP in the presence of endothelium but not in the endothelium‐denuded tissues. 5 Prazosin (5 μ m ) but not dibutyryl cyclic GMP (db‐cyclic GMP; 100 μ m ) blocked the hydrolysis of PI‐P 2 induced by 5 μ m NA. Synthesis of IP 3 induced by NA, as estimated with [ 3 H]‐inositol was not modified by application of 100 μ m db‐cyclic AMP or db‐cyclic GMP. 6 α‐Human atrial natriuretic peptide (α‐hANP; 0.1 μ m ) increased cyclic GMP in the presence or absence of endothelium. α‐hANP (0.1 μ m ) consistently inhibited the hydrolysis of PI‐P 2 induced by 5 μ m NA. 7 The results indicate that synthesis of IP 3 is inhibited neither by the synthesis of cyclic GMP in the cytosol nor by cyclic GMP itself. However, synthesis of IP 3 through hydrolysis of PI‐P 2 may be inhibited by an interaction between some steps in the IP 3 synthetic process and by the activation of the α‐hANP‐guanylate cyclase process at the sarcolemma.