Potentiation of PGE₂-mediated cAMP production during neuronal differentiation of human neuroblastoma SK-N-BE(2)C Cells

다국어 초록 (Multilingual Abstract)

Prostaglandin E₂(PGE₂) is an eicosanoid hormone produced by cyclooxygenases and isomerases from arachidonic acid. It elicits a various physiological responses including regulation of neurotransmitter release, the sleep-wake cycle, and body temperature. We have found that PGE₂ increases the production of cAMP in human neuroblastoma SK-N-BE(2)C cell. The PGE₂-induced cAMP generation was potentiated by muscarinic receptor-triggered intracellular Ca^(2+) increase, which reveals a cross-talk between prostanoid receptor and muscarinic receptor. Then, prostaglandin-evoked cAMP production was studied in SK-N-BE(2)C cell during the retinoic acid-induced neuronal differentiation. When stimulated with various kinds of prostaglandins, the potency order in cAMP production was PGE₁ = PGE₂ ＞ PGD₂ = PGF_(2α) = PGI₂. The incubation with 5 μM retinoic acid for 6 days promoted the morphological change(e. g. neurite formation) in SK-N-BE(2)C cells. After the differentiation, PGE₂-induced cAMP production was dramatically increased. The maximal effect was increased and half-effective concentration was reduced. The potency order among prostaglandins, however, was not changed during the differentiation. Misoprostol, EP2 receptor agonist, also increase cAMP level in a concentration dependent manner. Furthermore, EP2 receptor was detected by reverse transcription-polymerase chain reaction analysis and its mRNA level was increased about 7 times in differentiated cell with Northern blot analysis. These results suggest that the differentiation amplifies the expression of EP2 and subsequently increase PGE₂-evoked intracellular cAMP production in human neuroblastoma SK-N-BE(2)C cells.