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Endothelin and a Ca 2+ ionophore raise cyclic GMP levels in a neuronal cell line via formation of nitric oxide
Author(s) -
Reiser Georg
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.tb14147.x
Subject(s) - ionomycin , nitric oxide , endothelins , chemistry , arginine , endothelin receptor , veratridine , stimulation , endocrinology , medicine , biophysics , biochemistry , biology , receptor , sodium , amino acid , organic chemistry , sodium channel
1 The vasoconstrictor peptide endothelin‐1 caused a fast, transient rise in guanosine 3′:5′‐cyclic monophosphate (cyclic GMP) levels in a neuronal cell line (mouse neuroblastoma x rat glioma hybrid cells 108CC15). The mechanism of activation of guanylate cyclase by endothelin‐1 was investigated. The endothelin‐1‐induced rise depended on the release of internal Ca 2+ . 2 The stimulation of cyclic GMP synthesis induced by endothelin‐1 was suppressed after preincubating the cells in medium containing haemoglobin (IC 50 3 μ m ). Similarly, pretreatment of the cells with the l ‐arginine analogues, l ‐canavanine (IC 50 60 μ m ) or N G ‐monomethyl‐ l ‐arginine (IC 50 2.5 μ m ), inhibited the cyclic GMP response to endothelin‐1. Therefore, endothelin‐1 activates guanylate cyclase most probably via formation of nitric oxide, which is released from l ‐arginine. 3 The Ca 2+ ionophore ionomycin induced a transient rise in cyclic GMP levels, which was also suppressed by preincubation in the presence of either haemoglobin or the l ‐arginine analogues l ‐canavanine or N G ‐monomethyl‐ l ‐arginine. Therefore, we conclude that ionomycin can activate guanylate cyclase by a mechanism involving nitric oxide formation, similar to that induced by endothelin‐1. 4 The alkaloid veratridine, which activates Na + channels and also causes influx of Ca 2+ induced a transient rise of cyclic GMP levels in the neuronal cell line. This stimulation was blocked by pretreating the cells with l ‐canavanine, N G ‐monomethyl‐ l ‐arginine or haemoglobin. 5 Loading the cells with the Ca 2+ chelator BAPTA suppresed the cyclic GMP response to application of endothelin‐1, ionomycin, or veratridine. Thus, in the neuronal cell line a rise in cytosolic Ca 2+ activity seems to be sufficient to stimulate the nitric oxide forming enzyme which synthesizes the activator of soluble guanylate cyclase.