title: Evidence for endogenous agmatine in hypothalamo-neurohypophysial tract and its modulation on vasopressin release and Ca2+ channels.
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 microM 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 Ca(2+)-activated K(+) channel currents, agmatine (1-40 microM) inhibited Ca(2+) 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 IC(50)=4.6 microM. In the remaining (approximately 47%) neurohypophysial nerve terminals, only a higher (120 microM) concentration of agmatine could moderately inhibit Ca(2+) 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 Ca(2+) channel and, as a result, the release of AVP from neurohypophysial nerve terminals.
authors.affiliation: Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 411 East 69th Street, New York, NY 10021, USA. gaw2001@mail.med.cornell.edu
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Oleg S
authors.initials: OS
authors.lastname: Gorbatyuk
authors.forename: Govindan
authors.initials: G
authors.lastname: Dayanithi
authors.forename: Wei
authors.initials: W
authors.lastname: Ouyang
authors.forename: Jialing
authors.initials: J
authors.lastname: Wang
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Milner
authors.forename: Soundar
authors.initials: S
authors.lastname: Regunathan
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Reis
mesh_terms: D000376:Agmatine / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000032:analysis / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013495:Supraoptic Nucleus / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D014667:Vasopressins / Q000032:analysis / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D014667:Vasopressins; D000376:Agmatine