title: Tissue plasminogen activator and plasminogen are critical for osmotic homeostasis by regulating vasopressin secretion.
abstract: Systemic osmotic homeostasis is regulated mainly by neuroendocrine system of arginine-vasopressin (AVP) in mammalians. In the present study, we demonstrated that the immunoreactivity of tissue plasminogen activator (tPA) was observed specifically at neurosecretory granules of AVP-positive magnocellular terminals and that of plasminogen was seen at astrocytes in the neurohypophysis (NH). Both tPA and plasminogen knockout (KO) mice revealed higher plasma osmolarity upon water deprivation, a chronic osmotic stimulation, as compared with their wild-type (WT) animals, indicating abnormal osmotic control in these KO mice. tPA KO mice but not plasminogen ones revealed lower ability in secreting AVP into the blood circulation upon an acute osmotic stimulation. Both tPA and plasminogen KO animals showed lower ability in secreting AVP into the blood circulation upon a chronic osmotic stimulation. The recombinant tPA was able to promote the release of AVP from isolated NH. Chronic osmotic stimulation decreased the laminin expression level of neurohypophysial microvessel in WT mice but not in plasminogen KO ones. We suggest that AVP secretion is critically regulated by tPA-dependent facilitation of AVP release from terminals and plasminogen-dependent increase of AVP permeability across microvessels possibly via laminin degradation.
authors.affiliation: Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, Japan.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Imamura
authors.forename: Shoko
authors.initials: S
authors.lastname: Morita
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Okada
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ueshima
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuo
authors.forename: Seiji
authors.initials: S
authors.lastname: Miyata
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology; D024141:Collagen Type IV / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D007797:Laminin / Q000378:metabolism; D051379:Mice; D055806:Microvessels / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D009994:Osmolar Concentration; D010904:Pituitary Gland, Posterior / Q000098:blood supply / Q000378:metabolism / Q000648:ultrastructure; D010958:Plasminogen / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D014868:Water Deprivation / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D024141:Collagen Type IV; D007797:Laminin; D016760:Proto-Oncogene Proteins c-fos; D001127:Arginine Vasopressin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin