EP RECEPTOR SUBTYPES IMPLICATED IN THE PGE(2)-INDUCED SENSITIZATION OF POLYMODAL RECEPTORS IN RESPONSE TO BRADYKININ AND HEAT

1. Our previous studies, in which we used in vitro canine testis-sperm atic nerve preparations, showed that prostaglandin E(2) (PGE(2)) augme nts both bradykinin (BK)- and heat-induced discharges of polymodal rec eptors. However, the PGE(2) concentration required to augment the BK r esponses were 100 times lower than those necessary for the heat respon ses, suggesting that different receptors are involved in these phenome na. We studied which receptors for E series of prostaglandins (EP rece ptors) were responsible, using the antagonist and agonists for three s ubtypes of EP receptors. 2. PGE(2)-induced augmentation of the BK resp onses was unaffected when treated with an antagonist for the EP(1) rec eptor, AH6809. 3. An agonist for the EP(3) receptor, M&B28767, at grea ter than or equal to 10 nM, significantly augmented the BK responses i n a concentration-dependent manner that mimics the PGE(2)-induced effe ct. An agonist for the EP(1) receptor, 17-phenyl trinor PGE(2) (17-phe n PGE(2)), at the high concentrations of 0.1 and 1 mu M, augmented the BK responses in two and four of nine cases tested, respectively. Howe ver, this augmentation was not suppressed by the antagonist for the EP (1) receptor, AH6809. In addition, an agonist for the EP(2) receptor, butaprost, did not affect the BK responses even when applied at 10 mu M. 4. In contrast, butaprost at greater than or equal to 10 nM signifi cantly augmented the heat responses in a concentration-dependent manne r. M&B28767 and 17-phen PGE(2), respectively, augmented the heat respo nses at higher concentrations of 100 nM and 1 mu M. 5. These results i ndicate that the EP(3) and EP(2) receptor subtypes are differentially implicated in the respective PGE(2)-induced augmentation of BK respons es and heat responses of polymodal receptors.