Evidence for endogenous agmatine in hypothalamo-neurohypophysial tract and its modulation on vasopressin release and Ca2+ channels

Academic Article

Abstract

  • Agmatine, decarboxylated from arginine by arginine decarboxylase, is particularly prominent in the hypothalamus. The present study utilized the rat hypothalamo-neurohypophysial system to determine expression and 'pre-synaptic' modulation of agmatine in the central nervous system (CNS). Under confocal-laser scanning, agmatine-like immunoreactivity (Agm-LI) was found enriched in arginine-vasopressin (AVP)-containing magnocellular neurons of the supraoptic nuclei (SON) and paraventricular nuclei (PVN). In addition, using electron microscopy, Agm-LI was found closely associated with large neurosecretory-like vesicles in neurohypophysial nerve terminals of posterior pituitary gland. Radioimmunoassay revealed that 10 and 30 μM agmatine concentration-dependently inhibited the depolarization-evoked AVP release from isolated neurohypophysial terminals. Using perforated patch-clamp, effects of agmatine on whole-terminal voltage-gated ion currents in the isolated neurohypophysial nerve terminals were examined. While it did not significantly affect either tetrodotoxin (TTX)-sensitive Na+ or sustained Ca2+-activated K+ channel currents, agmatine (1-40 μM) inhibited Ca2+ channel currents in approximately 53% of the total nerve terminals investigated. The onset of inhibitory effect was immediate, and the inhibition was reversible and concentration-dependent with an IC50=4.6 μM. In the remaining (approximately 47%) neurohypophysial nerve terminals, only a higher (120 μM) concentration of agmatine could moderately inhibit Ca2+ channel currents. The results suggest that: (1) endogenous agmatine is co-expressed in AVP-containing, hypothalamic magnocellular neurons of the SON/PVN and in neurohypophysial nerve terminals of posterior pituitary gland; (2) agmatine may serve as a physiological neuromodulator by regulating the voltage-gated Ca2+ channel and, as a result, the release of AVP from neurohypophysial nerve terminals. © 2002 Elsevier Science B.V. All rights reserved.
  • Authors

    Published In

  • Brain Research  Journal
  • Digital Object Identifier (doi)

    Author List

  • Wang G; Gorbatyuk OS; Dayanithi G; Ouyang W; Wang J; Milner TA; Regunathan S; Reis DJ
  • Start Page

  • 25
  • End Page

  • 36
  • Volume

  • 932
  • Issue

  • 1-2