NEUROENDOCRINOLOGY
LETTERS including Psychoneuroimmunology, Neuropsychopharmacology,
Reproductive Medicine, Chronobiology
and
Human Ethology
ISSN 0172–780X
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
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.
