PMID- 11948662 OWN - NLM STAT- MEDLINE DCOM- 20020503 LR - 20191210 IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 68 IP - 2 DP - 2002 Apr 15 TI - Phosphatidylinositol kinase enzymes regulate the retrograde axonal transport of NT-3 and NT-4 in sympathetic and sensory neurons. PG - 169-75 AB - Phosphatidylinositol 3-kinase (PI3-kinase) and phosphatidylinositol 4-kinase (PI4-kinase) enzymes are an important family of signaling molecules that have been implicated in the regulation of intracellular vesicle trafficking. It has previously been shown that PI3-kinase and PI4-kinase enzymes regulate neuronal survival and the retrograde axonal transport of nerve growth factor in sympathetic and sensory neurons. We have extended these studies to examine the role these enzymes play in the regulation of the retrograde axonal transport of neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) in sympathetic and sensory neurons in vivo. Wortmannin (0.1 nmol/eye), a PI3-kinase and PI4-kinase antagonist, reduced the amount of (125)I-NT-3 retrograde transport in sympathetic neurons by approximately 50% and (125)I-NT-4 in sympathetic neurons by approximately 40% and sensory neurons by approximately 20%. The PI3-kinase antagonist LY294002 (100 nmol/eye) reduced the retrograde axonal transport of (125)I-NT-4 in sympathetic and sensory neurons, and (125)I-NT-3 in sympathetic neurons. Phenylarsine oxide (PAO), a PI4-kinase antagonist, significantly inhibited (125)I-NT-4 retrograde axonal transport in sympathetic and sensory neurons. These results show that wortmannin-sensitive PI3-kinases and PI4-kinases may be involved in NT-3 and NT-4 retrograde axonal transport. The retrograde axonal transport of neurotrophic factors in sympathetic and sensory neurons in vivo appears to depend upon the activation of different receptors and second messenger cascades at the nerve terminal. CI - Copyright 2002 Wiley-Liss, Inc. FAU - Bartlett, Selena E AU - Bartlett SE AD - Division of Neuroscience, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia. FAU - Reynolds, Anna J AU - Reynolds AJ FAU - Weible, Michael 2nd AU - Weible M 2nd FAU - Hendry, Ian A AU - Hendry IA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (AG-879) RN - 0 (Androstadienes) RN - 0 (Arsenicals) RN - 0 (Chromones) RN - 0 (Enzyme Inhibitors) RN - 0 (Morpholines) RN - 0 (Nerve Growth Factors) RN - 0 (Neurotrophin 3) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Tyrphostins) RN - 0HUR2WY345 (oxophenylarsine) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - EC 2.7.10.1 (Receptor, trkA) RN - P658DCA9XD (neurotrophin 4) RN - XVA4O219QW (Wortmannin) SB - IM MH - Androstadienes/pharmacology MH - Animals MH - Arsenicals/pharmacology MH - Axonal Transport/drug effects/*physiology MH - Biological Transport, Active/drug effects/*physiology MH - Chromones/pharmacology MH - Enzyme Inhibitors/pharmacology MH - Female MH - Iris/innervation MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Morpholines/pharmacology MH - Nerve Growth Factors/metabolism MH - Neurons/*metabolism MH - Neurons, Afferent/*metabolism MH - Neurotrophin 3/metabolism MH - Phosphatidylinositol 3-Kinases/*physiology MH - Phosphoinositide-3 Kinase Inhibitors MH - Receptor, trkA/antagonists & inhibitors MH - Sympathetic Nervous System/cytology/*metabolism MH - Tyrphostins/pharmacology MH - Wortmannin EDAT- 2002/04/12 10:00 MHDA- 2002/05/04 10:01 CRDT- 2002/04/12 10:00 PHST- 2002/04/12 10:00 [pubmed] PHST- 2002/05/04 10:01 [medline] PHST- 2002/04/12 10:00 [entrez] AID - 10.1002/jnr.10201 [pii] AID - 10.1002/jnr.10201 [doi] PST - ppublish SO - J Neurosci Res. 2002 Apr 15;68(2):169-75. doi: 10.1002/jnr.10201.