Characteristics of acid extrusion from Chinese hamster ovary cells expressing different prostaglandin EP receptors

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• 作者：Yuichi Okada ; Takanobu Taniguchi ; Shigeru Morishima ; Fumiko Suzuki ; Yoshio Akagi and Ikunobu Muramatsu
• 关键词：Extracellular acidification ; EP receptor ; Prostaglandin E₂ ; Na⁺/H⁺ exchanger (NHE) ; Microphysiometer
• 刊名：Life Sciences
• 出版年：2006
• 出版时间：18 April 2006
• 年：2006
• 卷：78
• 期：21
• 页码：2454-2462
• 全文大小：312 K

文摘

Acid extrusion responses to prostaglandin E₂ were investigated in Chinese hamster ovary (CHO) cells heterologously expressing human EP₁, EP₂, and EP_3I receptors (hEP₁, hEP₂ and hEP_3I) by using a microphysiometer that detected small pH changes in the extracellular microenvironment. In the cells expressing hEP₁, which is known to increase intracellular Ca²⁺, prostaglandin E₂ (1 and 10 nM) slowly accelerated acid extrusion, but at higher concentrations an initial transient phase (approximately 5 times greater than the basal acidification) overlapped the slowly developing phase. In contrast, the cells expressing hEP₂, which evokes cAMP production, showed dual responses to prostaglandin E₂: an initial reduction followed by an acceleration of acid extrusion. In the cells expressing hEP_3I, which is known to produce both a decrease in cAMP and a modest increase in intracellular Ca²⁺, acid extrusion was gradually accelerated by prostaglandin E₂ and reached a plateau at around 2 min. Elimination of extracellular Ca²⁺ diminished the responses to prostaglandin E₂ in hEP₁ cells, but had little effect on the responses in hEP₂ and hEP_3I cells. Forskolin mimicked the dual effects of prostaglandin E₂ observed in the hEP₂ cells. Pretreatment with pertussis toxin inhibited the response to prostaglandin E₂ in hEP_3I cells, but the responses in hEP₁ and hEP₂ cells were not affected. Na⁺/H⁺ exchanger (NHE) inhibitors (EIPA and HOE642) suppressed all the responses induced by prostaglandin E₂ in hEP₁, hEP₂, and hEP_3I cells. These results suggest that EP receptor subtypes regulate acid extrusion mainly via NHE-1 through distinct signal transduction pathways in CHO cells.