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Inhibition of Dopamine Release by Prostaglandin EP3 Receptor via Pertussis Toxin‐Sensitive and ‐Insensitive Pathways in PC12 Cells
Author(s) -
Nakamura Kazuhiro,
Katoh Hironori,
Ichikawa Atsushi,
Negishi Manabu
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71020646.x
Subject(s) - pertussis toxin , neurotransmitter , ionomycin , forskolin , agonist , medicine , endocrinology , receptor , dopamine , chemistry , biology , g protein , biochemistry , stimulation
Prostaglandin EP3 receptor is involved in the inhibition of neurotransmitter release from presynaptic nerve terminals in various tissues. We have examined the regulation of neurotransmitter release by the EP3 receptor using a PC12 cell line that stably expresses the EP3B receptor isolated from bovine adrenal medulla. In the cells, M&B28767, an EP3 agonist, inhibited the 50 m M KCl‐ or 10 n M bradykinin‐induced [ 3 H]dopamine release in a concentration‐dependent manner (10 p M to 0.1 µ M ). This inhibition was partially reversed by pretreatment with pertussis toxin, whereas under the same condition, the agonist‐induced inhibition of forskolin‐stimulated cyclic AMP accumulation was suppressed completely. In contrast, M&B28767 did not affect the high K + ‐ or bradykinin‐induced increase in intracellular Ca 2+ concentration. Moreover, M&B28767 also inhibited the [ 3 H]dopamine release induced by the Ca 2+ ionophore ionomycin, and this inhibition was also partially reversed by pretreatment with pertussis toxin. These results indicate that the EP3 receptor is coupled to dual pathways, pertussis toxin‐sensitive and ‐insensitive G‐protein pathways, to regulate neurotransmitter release without changing Ca 2+ influx in neuronal cells.