Abstract
Prostaglandin E2 (PGE2) and substance P (SP) have been reported to induce massive Cl− secretion in the guinea pig distal colon. It has been reported that this synergistic action of PGE2 and SP is occurred by crosstalk between cAMP and Ca2+ second messenger systems via each receptor in epithelial cells. In the present study, we pharmacologically and histologically identified the PGE2 receptors (EP1-4 and DP receptors) for the synergistic Cl− secretion in the guinea pig distal colon. In pharmacological experiments, mucosa-submucosal preparations of guinea pig distal colon were mounted in Ussing chamber, and short-circuit current (Isc) was measured as an index of ion transport across the epithelium. All the experiments were performed in the presence of tetrodotoxin and piroxicam to remove the influence of neurons and endogenous prostaglandin production. As a result, EP2 and DP receptor subtypes were predominant receptors for synergistic action of PGE2 and SP. In immunohistochemistry, EP2 receptor-immunoreactivity (-IR) was observed in almost all epithelial membrane in the guinea pig distal colon. EP4 receptor-IR was observed in some epithelial cells. On the other hand, EP1 and EP3 receptor-IRs were not observed in mucosa. These results of immunohistochemistry are consistent with the pharmacological results. Therefore, the present study indicates that EP2 receptors on epithelial membrane contribute to the synergistic Cl− secretion by PGE2 and SP. [Jpn J Physiol 54 Suppl:S89 (2004)]
