Gi-coupled prostanoid receptors are the likely targets for COX-1-generated prostanoids in rat pheochromocytoma (PC12) cells.
Cyclooxygenase-1 (COX-1) behaves as a delayed response gene in rat pheochromocytoma (PC12) cells exposed to nerve growth factor (NGF). To investigate the possible targets for COX-1 generated prostanoids in the early stages of neuronal differentiation, we have examined the expression of prostanoid receptors by PC12 cells using functional assays. Prostanoid receptor-specific agonists failed to activate adenylyl cyclase in undifferentiated and NGF-treated PC12 cells; neither did they stimulate phospholipase C activity. EP3 receptor agonists and PGF(2alpha) were the only active ligands, able to inhibit forskolin-stimulated adenylyl cyclase activity. PC12 cells expressed EP3 and FP receptor mRNA, but only the responses to EP3 receptor agonists were inhibited by the EP3 receptor antagonist ONO-AE3-240. The functional role of NGF-stimulated COX-1 remains to be determined since we found no strong evidence of a role for EP3 receptors in the morphological changes induced by NGF during the early stages of differentiation of PC12 cells.
Yung
H S
HS
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
Chow
Kevin B S
KB
Lai
K H
KH
Wise
H
H
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000096:biosynthesis; D020932:Nerve Growth Factor / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000502:physiology*; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D058308:Receptors, Prostaglandin E, EP3 Subtype
C545649:Ptger3 protein, rat; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D020932:Nerve Growth Factor; D051545:Cyclooxygenase 1; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D015232:Dinoprostone