Functional role of prostacyclin receptor in rat dorsal root ganglion neurons.
Recent studies on prostanoids showed that some of prostanoid receptors are expressed in rat dorsal root ganglion (DRG) neurons. These facts suggest that prostanoid receptors might be involved in the excitation mechanism of DRG neurons. In the present study, PCR experiments revealed that one of prostanoid receptor, prostacyclin receptor (IP receptor) was expressed in L6 and S1 rat DRG neurons and that the expression of IP receptor was not changed in DRG neurons obtained from the cyclophosphamide (CYP)-induced cystitis rat. We examined the functional role of IP receptor agonist and other prostanoids by measuring cyclic AMP (cAMP) accumulation and substance P (SP) release in primary cultured DRG neurons. The pretreatment of DRG neurons with prostanoid agonists such as iloprost (IP), butaprost (EP(2)), misoprostol (EP(2-4)), PGE(2) (EP(1-4)) or PGD(2) (DP and CRTH2) sensitized the DRG neurons and hence potentiated the lys-bradykinin-induced SP release. The increase of SP release by lys-BK plus prostanoid agonists was proportion to cAMP accumulation. Iloprost was the most potent agonist to induce cAMP accumulation and SP release among prostanoid agonists evaluated in this study and its effect is mediated by IP receptor. Moreover, capsaicin-, ATP- and KCl-induced SP release was also enhanced by iloprost although iloprost did not change intracellular Ca(2+) and membrane depolarization induced by these chemical stimuli. These results strongly indicate that IP receptor play an important role in the sensitization of rat sensory neuron.
Nakae
Koichi
K
TRA Urology, Research Center Kyoto, Bayer Yakuhin, Ltd., 6-5-1-3 Kunimidai, Kizu-cho, Soraku-gun, Kyoto 619-0216, Japan. nakaek@bikaken.or.jo
Hayashi
Fumihiko
F
Hayashi
Mayumi
M
Yamamoto
Noriyuki
N
Iino
Takashi
T
Yoshikawa
Satoru
S
Gupta
Jang
J
D000818:Animals; D000831:Animals, Newborn; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D018856:Cystitis, Interstitial / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016285:Iloprost / Q000494:pharmacology; D018836:Inflammation Mediators / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D011189:Potassium Chloride / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044006:Receptors, Epoprostenol / Q000819:agonists / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D018836:Inflammation Mediators; D011453:Prostaglandins; D044006:Receptors, Epoprostenol; D014665:Vasodilator Agents; D013373:Substance P; D011189:Potassium Chloride; D000242:Cyclic AMP; D016285:Iloprost; D002211:Capsaicin