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Evidence for endogenous agmatine in hypothalamo-neurohypophysial tract and its modulation on vasopressin release and Ca2+ channels.
- Source :
-
Brain research [Brain Res] 2002 Apr 05; Vol. 932 (1-2), pp. 25-36. - Publication Year :
- 2002
-
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.
- Subjects :
- Agmatine analysis
Agmatine pharmacology
Animals
Calcium Channels analysis
Hypothalamo-Hypophyseal System chemistry
Hypothalamo-Hypophyseal System ultrastructure
Male
Neurons chemistry
Neurons ultrastructure
Paraventricular Hypothalamic Nucleus chemistry
Paraventricular Hypothalamic Nucleus physiology
Paraventricular Hypothalamic Nucleus ultrastructure
Rats
Rats, Sprague-Dawley
Supraoptic Nucleus chemistry
Supraoptic Nucleus physiology
Supraoptic Nucleus ultrastructure
Vasopressins analysis
Agmatine metabolism
Calcium Channels physiology
Hypothalamo-Hypophyseal System physiology
Neurons physiology
Vasopressins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-8993
- Volume :
- 932
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 11911858
- Full Text :
- https://doi.org/10.1016/s0006-8993(02)02260-6