TY - JOUR
T1 - Bradykinin Receptor‐Mediated Cyclic GMP Formation in a Nerve Cell Population (Murine Neuroblastoma Clone N1E‐115)
AU - Snider, R. Michael
AU - Richelson, Elliott
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1984/12
Y1 - 1984/12
N2 - A clone of murine neuroblastoma (N1E‐115) was shown to have functional receptors for the nonapeptide bradykinin. These receptors mediated a large, rapid (about 1 min to peak) and calcium‐dependent increase in cyclic GMP. The median effective concentration (EC50) averaged 1.4 nM. In addition, this event was inhibited by quinacrine, 5,8,11,14‐eicosatetraynoic acid, and nordi‐hydroguaiaretic acid, suggesting involvement of phospholipase A2 with subsequent formation of lipoxygenase metabolites of arachidonic acid. [3H]Bradykinin binding to intact cells, investigated under conditions nearly identical to those used in the cyclic GMP assay, yielded binding sites with KDs of 0.83 pM, 1.0 nM, and 4.9 nM with respective Bmax values of 12, 160, and 250 fmol/106 cells. Apparently, the cyclic GMP response was associated with the binding site in which the KD= 1.0 nM. Peptide analogs of bradykinin stimulated cyclic GMP with EC50s nearly identical to their respective KDs determined in binding assays with [3H]bradykinin, thus providing evidence for receptor specificity of this response. This finding of a biochemical response of bradykinin promises to make N1E‐115 cells a convenient model system for study of neuronal bradykinin receptors.
AB - A clone of murine neuroblastoma (N1E‐115) was shown to have functional receptors for the nonapeptide bradykinin. These receptors mediated a large, rapid (about 1 min to peak) and calcium‐dependent increase in cyclic GMP. The median effective concentration (EC50) averaged 1.4 nM. In addition, this event was inhibited by quinacrine, 5,8,11,14‐eicosatetraynoic acid, and nordi‐hydroguaiaretic acid, suggesting involvement of phospholipase A2 with subsequent formation of lipoxygenase metabolites of arachidonic acid. [3H]Bradykinin binding to intact cells, investigated under conditions nearly identical to those used in the cyclic GMP assay, yielded binding sites with KDs of 0.83 pM, 1.0 nM, and 4.9 nM with respective Bmax values of 12, 160, and 250 fmol/106 cells. Apparently, the cyclic GMP response was associated with the binding site in which the KD= 1.0 nM. Peptide analogs of bradykinin stimulated cyclic GMP with EC50s nearly identical to their respective KDs determined in binding assays with [3H]bradykinin, thus providing evidence for receptor specificity of this response. This finding of a biochemical response of bradykinin promises to make N1E‐115 cells a convenient model system for study of neuronal bradykinin receptors.
KW - Arachidonic acid
KW - Bradykinin
KW - Cyclic GMP
KW - Lipoxygenase
KW - Murine neuroblastoma clone N1E‐115
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U2 - 10.1111/j.1471-4159.1984.tb06104.x
DO - 10.1111/j.1471-4159.1984.tb06104.x
M3 - Article
C2 - 6149270
AN - SCOPUS:0021744677
SN - 0022-3042
VL - 43
SP - 1749
EP - 1754
JO - Journal of neurochemistry
JF - Journal of neurochemistry
IS - 6
ER -