Signaling involved in pituitary adenylate cyclase-activating polypeptide-stimulated ADNP expression.
Activity-dependent neurotrophic protein (ADNP) was discovered as a novel response gene for VIP and has neuroprotective potential. When the VIP paralog, PACAP38 was added to mouse neuron-glia co-cultures, it induced ADNP mRNA expression in a bimodal fashion at subpico- and nanomolar concentrations with greater response at subpicomolar level. The response was attenuated by a PAC1-R antagonist at both concentrations and by a VPAC1-R antagonist at nanomolar concentration only. An IP3/PLC inhibitor attenuated the response at both concentrations of PACAP38, but a MAPK inhibitor had no effect. A PKA inhibitor suppressed the response at nanomolar concentration only. These findings suggest that ADNP expression is mediated through multiple receptors and signaling pathways that are regulated by different concentrations of PACAP.
U.S.-Japan Biomedical Research Laboratories, Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Tomoya
T
Nakamachi
Min
M
Li
Seiji
S
Shioda
Akira
A
Arimura
D000818:Animals; D018920:Coculture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000737:chemistry; D020935:MAP Kinase Signaling System; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000737:chemistry; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000037:antagonists & inhibitors; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000037:antagonists & inhibitors; D015398:Signal Transduction
C117632:Adnp protein, mouse; D004791:Enzyme Inhibitors; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I