The STC-1 cells express functional orexin-A receptors coupled to CCK release.
Orexins are newly discovered neuropeptides regulating feeding and vigilance and have been detected in neuroendocrine cells of the gut. Potential neuroendocrine functions of orexin are unknown. Therefore, the effects of orexin-A on the intestinal neuroendocrine cell line, STC-1, were investigated as a model system. RT-PCR demonstrated the presence of both OX(1) and OX(2) receptors. Stimulation with orexin-A produced a dose-dependent release of cholecystokinin (CCK), which was abolished by removal of extracellular Ca(2+) or the presence of the voltage-gated L-type Ca(2+)-channel blocker diltiazem (10 microM). Orexin-A (Ox-A) elevated intracellular Ca(2+), which was dependent on extracellular Ca(2+). Furthermore, orexin-A caused a membrane depolarization in the STC-1 cells. Ox-A neither elevated cAMP levels nor stimulated phosphoinositide turnover in these cells. These data demonstrate a functional orexin receptor in the STC-1 cell line. Ox-A produces CCK release in these cells, by a mechanism involving membrane depolarization and subsequently activation of L-type voltage-gated Ca(2+)-channels.
Larsson
K P
KP
The Cell Biology, Research Group, Department of Neurobiology, University of Kuopio, FIN-70211 Kuopio, Finland.
Akerman
K E
KE
Magga
J
J
Uotila
S
S
Kukkonen
J P
JP
Näsman
J
J
Herzig
K H
KH
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002766:Cholecystokinin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009479:Neuropeptides / Q000378:metabolism; D064446:Orexin Receptors; D000068797:Orexins; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000096:biosynthesis* / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013050:Spectrometry, Fluorescence
D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D007295:Inositol Phosphates; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D010455:Peptides; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D002766:Cholecystokinin; D000242:Cyclic AMP; D004110:Diltiazem; D002118:Calcium