Membrane depolarization by activation of prostaglandin E receptor EP3 subtype of putative serotonergic neurons in the dorsal raphe nucleus of the rat.
A whole-cell current-clamp study using a thin slice preparation of the rat brain was carried out to elucidate the function of prostaglandin E (PGE) receptor EP3 subtype in the dorsal raphe nucleus (DR), where mRNA of this subtype is highly expressed. Bath application of PGE2 or M&B 28767, an EP3 agonist, depolarized the membrane of the large DR neurons in a concentration-dependent manner between 10(-9) and 10(-6) M. These neurons showed hyperpolarization of membrane potential to 10 or 50 microM serotonin. Neither an EP2 receptor agonist, butaprost, an EP2/EP4 receptor agonist, 11-deoxy-PGE1, nor an EP1 receptor agonist, 17-phenyl-PGE2, had any effect on large DR neurons between 10(-9) and 10(-6) M. The M&B 28767-induced depolarization was observed in a Ca(2+)-free, high Mg2+ (5 mM) solution containing 0.3 microM tetrodotoxin, and occurred equally well when intracellular Cl- was replaced by gluconate. These results suggest that direct agonist-activation of EP3 receptor depolarizes the membrane by a cationic conductance, leading to excitation of DR neurons, and indicate a physiological implication that EP3 receptor may modulate the serotonergic inhibition of neuronal activities.
Momiyama
T
T
Department of Pharmacology, Kyoto University, Japan.
Todo
N
N
Sugimoto
Y
Y
Ichikawa
A
A
Narumiya
S
S
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D010120:Oxytocics / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000187:drug effects*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D010120:Oxytocics; D011459:Prostaglandins E, Synthetic; C545649:Ptger3 protein, rat; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C032405:11-deoxy-16-phenoxy-17,18,19,20-tetranorprostaglandin E1; D000527:Alprostadil; D015232:Dinoprostone