October 28, 2002
NEL HOME, Newsletter
Z.KLEIN AWARD for Human Ethology
CONTENTS Vol.23 No.4 Aug 2002
VOL.22, 2001
VOL.21, 2000
VOL.20, 1999
VOL.19, 1998
VOL.18, 1997

including Psychoneuroimmunology, Neuro
Reproductive Medicine, Chronobiology
and Human Ethology
ISSN 0172–780X

NEL Vol.23 No.4, August 2002


2002; 23:273-280
pii: NEL230402R01
PMID: 12195224

Free full text online pdf [421 kb]
purchace & print HERE

Multifaceted purinergic regulation of stimulus-secretion coupling in the neurohypophysis
Jean-Denis Troadec 1 & Sylvie Thirion 2

1. Lab Steroids and Nervous System, INSERM U488, Kremlin Bicêtre, France.
2. Lab. Physiology and Physiopathology, UMR CNRS 7079, Paris, France.

Key words:
neurohypophysis; ATP; adenosine; purinergic receptor; vasopressin; oxytocin; nerve terminals; neurohypophysial astrocytes; autocrine/paracrine feedback

Submitted: July 12, 2002
Accepted: July 14, 2002


The neurohypophysis is an original model of the CNS secretory system releasing vasopressin (AVP) and oxytocin (OXT), two neuropeptides hormones synthesized by the magnocellular neurons of the hypothalamus. Specific patterns of action potentials originating from cellular bodies of magnocellular neurons control the release of AVP and OT, but intra-neurohypophysis regulations do modulate the neuropeptides release. There is now good evidence for the effects of extracellular purines in the control of neurohypophysial secretion. This paper brings together evidence for the multiple, intricate actions of purines in the extracellular space of the neurohypophysis. It covers four main points. First, the activity-dependent release of endogenous ATP in the neurohypophysis. Second, the action of ATP on both neuronal and non-neuronal compartments of the neural lobe. Third, the termination of ATP positive feedback by ecto-nucleotidases. And finally the possible involvement of adenosine in the regulation of neurohypophysial secretion and glial plasticity. The data suggest that ATP and adenosine are physiological modulators of the release of neurohypophysial peptides by acting directly on nerve terminals and indirectly on neurohypophysial astrocytes. Since purinergic receptors are widespread in nervous and endocrine systems, the neurohypophysis appears as an useful model for studying the role of purines in the regulation of stimulus-secretion coupling and neuron-glia interactions. The feedback mechanisms found in the neurohypophysis could be ubiquitous, occurring throughout the central nervous system and in other secretory systems.


Introduction ATP, besides the function of intracellular energy source, appears as an extracellular signal in a wide variety of systems where it is involved in both physiological and physiopathological conditions [reviewed in 1]. ATP acts as a neurotransmitter in the central and peripheral nervous systems. The co-storage of ATP with acethylcholine and catecholamines has been demonstrated for a variety of peripheral and central synaptic vesicles [2]. ATP co-released with these neurotransmitters can act as fast excitatory agent on both cholinergic [3] and adrenergic [4] neurons. Furthermore, ATP influences endocrine systems, where it can modulate hormones release [5 & 6]. The extracellular actions of ATP are mediated by specific membrane located receptors referred as P2 receptors. Based on the cloning of P2 receptors, two subtypes were defined as P2X the ligand-gated ion channel and P2Y the G protein-coupled receptor [7]. Adenosine, which is produced by hydrolysis of ATP by ecto-nucleotidases, may also act as a neuromodulator within the nervous system. It modulates the release of neurotransmitters [8], post-synaptic responsiveness [9], and the action of other receptors systems [10]. Specific receptors referred as P1 receptors and subdivided in different subtypes (A1, A2A, A2B and A3) intercede in the different actions of adenosine. The actions of both ATP and adenosine in the nervous system are not restricted to neurons, as several glial cells including astrocytes, microglia, oligendendrocytes and Schwann cells bear functional P2 and P1 purinergic receptors [11]. Moreover, data obtained in vitro indicate that extracellular purines control astrocyte proliferation and the production of trophic factors by glial cells [12]. The neurohypophysis contains vasopressin (AVP) and oxytocin (OXT) releasing neurosecretory endings originating from magnocellular neurons of the hypothalamus [13]. This system has been used to demonstrate the direct relationship between intracellular calcium increase and neurohormone secretion [14] and it is considered as an unique model for studying the regulation of stimulus-secretion. Although the release of the neuropeptides is driven by specific patterns of action potentials initiated by hypothalamic neurons, intrinsic regulations can modulate the hormone release at the neurohypophysis level [15]. Moreover, several lines of evidence strongly indicate that glia participates in the control of neurohypophysial secretion [13]. Consequently, this organ appears therefore as an excellent model for studying the role of extracellular purines in the regulation of secretion and for examining the involvement of these compounds in the control of secretion by glia. This paper summarizes our research data and results of the literature indicating the multiple, complicated feedback regulatory mechanisms by which purines control neuroendocrine stimulus-secretion coupling.

... ...

Copyright  Neuroendocrinology Letters 2002
All rights reserved. No part may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or ortherwise, without prior written permission from the Editor-in-Chief.