Schwann cells express IP prostanoid receptors coupled to an elevation in intracellular cyclic AMP.
We have shown previously that prostaglandin E(2) (PGE(2)) and prostaglandin I(2) (PGI(2)) are each produced in an explant model of peripheral nerve injury. We report that IP prostanoid receptor mRNA and protein are present in primary rat Schwann cells. IP prostanoid receptor stimulation using prostacyclin produced an elevation in intracellular cyclic AMP concentration ([cAMP](i)) in primary Schwann cells. Peak [cAMP](i) was observed between 5-15 min of stimulation followed by a gradual recovery toward basal level. Phosphorylation of cyclic AMP-response element binding protein (CREB) on Ser(133) was also detected after IP prostanoid receptor stimulation and CREB phosphorylation was inhibited completely by the protein kinase A inhibitor, H-89. Intracellular calcium levels were not affected by IP prostanoid receptor stimulation. Unlike forskolin, IP prostanoid receptor stimulation did not significantly augment Schwann cell proliferation in response to growth factor treatment. However, IP prostanoid receptor stimulation increased the number of Schwann cells that were able to generate a calcium transient in response to P2 purinergic receptor activation. These findings suggest that signaling via the IP prostanoid receptor may by relevant to Schwann cell biology in vivo.
Muja
Naser
N
Neuroscience Program, Loyola University of Chicago, Maywood, Illinois, USA.
Nelson
Julie K
JK
DeVries
George H
GH
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors; D011464:Epoprostenol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism*; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology; D012694:Serine / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010975:Platelet Aggregation Inhibitors; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; D012694:Serine; D011464:Epoprostenol; D000242:Cyclic AMP; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002118:Calcium