PMID- 16150423 OWN - NLM STAT- MEDLINE DCOM- 20090126 LR - 20181201 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1058 IP - 1-2 DP - 2005 Oct 5 TI - Matrix-degrading enzymes tissue plasminogen activator and matrix metalloprotease-3 in the hypothalamo-neurohypophysial system. PG - 1-9 AB - The hypothalamo-neurohypophysial system (HNS), synthesizing arginine vasopressin (AVP) and oxytocin (OXT), is well known to show structural plasticity during chronic physiological stimulation such as salt loading and lactation. In the present study, we undertook in the HNS to study localization and activity-dependent changes in the expression of matrix-degrading enzymes such as tissue plasminogen activator (tPA) and matrix metalloprotease-3 (MMP-3). Double labeling confocal microscopy demonstrated that the immunoreactivity of tPA was localized at AVP-positive dendrites in the supraoptic nucleus (SON) and AVP-positive terminals in the neurohypophysis (NH). The immunoreactivity of tPA was also seen at astrocytic processes in the HNS. Likewise, the immunoreactivity of MMP-3 was observed at AVP-positive dendrites and terminals. High magnification observation further revealed punctate distribution of tPA and MMP-3 immunoreactivity at dendrites and terminals, suggesting that they are localized at neurosecretory granules. Salt loading, known as the chronic stimulation to cause the structural plasticity, increased protein and mRNA levels of tPA in the SON but reduced protein levels of it in the NH. The chronic stimulation also increased protein levels of urokinase plasminogen activator in the SON, but the stimulation did not change protein levels of MMP-3 in the SON and NH. Depolarizing agent KCl released tPA from isolated neurosecretosomes, and this depolarization-dependent release was abolished by verapamil, a Ca(2+) channel blocker. These results demonstrate that tPA and MMP-3 are localized mainly at dendrites and terminals of AVP-expressing magnocellular neurons and tPA is released in an activity-dependent manner, suggesting that matrix-degrading proteases are candidate molecules to be concerned with the structural plasticity in the HNS. FAU - Miyata, Seiji AU - Miyata S AD - Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Kyoto, Japan. smiyata@kit.ac.jp FAU - Nakatani, Yoshihiro AU - Nakatani Y FAU - Hayashi, Noriko AU - Hayashi N FAU - Nakashima, Toshihiro AU - Nakashima T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050916 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (RNA, Messenger) RN - 113-79-1 (Arginine Vasopressin) RN - 660YQ98I10 (Potassium Chloride) RN - EC 3.4.21.68 (Tissue Plasminogen Activator) RN - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Animals MH - Arginine Vasopressin/metabolism MH - Dendrites/enzymology/ultrastructure MH - Hypothalamo-Hypophyseal System/cytology/*enzymology/metabolism MH - Immunohistochemistry MH - Male MH - Matrix Metalloproteinase 3/*metabolism MH - Membrane Potentials/drug effects/physiology MH - Microscopy, Confocal MH - Neuronal Plasticity/physiology MH - Neurons/cytology/*enzymology/metabolism MH - Pituitary Gland, Posterior/cytology/*enzymology/metabolism MH - Potassium Chloride/pharmacology MH - Presynaptic Terminals/enzymology/ultrastructure MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Wistar MH - Secretory Vesicles/metabolism/ultrastructure MH - Supraoptic Nucleus/cytology/enzymology MH - Tissue Plasminogen Activator/genetics/*metabolism MH - Up-Regulation/physiology MH - Urokinase-Type Plasminogen Activator/metabolism EDAT- 2005/09/10 09:00 MHDA- 2009/01/27 09:00 CRDT- 2005/09/10 09:00 PHST- 2005/04/13 00:00 [received] PHST- 2005/07/08 00:00 [revised] PHST- 2005/07/13 00:00 [accepted] PHST- 2005/09/10 09:00 [pubmed] PHST- 2009/01/27 09:00 [medline] PHST- 2005/09/10 09:00 [entrez] AID - S0006-8993(05)01059-0 [pii] AID - 10.1016/j.brainres.2005.07.027 [doi] PST - ppublish SO - Brain Res. 2005 Oct 5;1058(1-2):1-9. doi: 10.1016/j.brainres.2005.07.027. Epub 2005 Sep 16.