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VOL. 74 (3), 387-408, 2008 FINE TUNING NEUROMODULATION BY ADENOSINE...
be more effective than A1 receptors in high frequency stimulation
(7), and in 2003 when it was demonstrated that A2A receptors are
more effective than A1 receptors in aged than in young rats (see 31).
It appears that whilst the most predominant action of extracellular
adenosine in the hippocampus is A1-receptor mediated inhibition of
synaptic transmission, the less abundant A2A-receptor are devoted to:
prime, trigger or modulate the action and/or inactivation of other
neuromodulators and, therefore, to fine-tune neuronal activity (37).
Other interesting observations on A2A effects include stimulation by
A2A-receptors of the carotid body arterial chemoreceptors and
ventilation. Since hypoxia is the physiological stimuli of carotid body
chemoreceptors, the finding that a substance, preferentially released
by hypoxia-adenosine, stimulates ventilation seems to close a circle
of understanding the mechanisms involved in hypoxic stimulation of
ventilation (20, 21).
ADENOSINE AND NEUROPROTECTION
What means neuroprotection?
It is a collective therapeutic approach to provide neuronal
survival. In a normal neuron the amount of O2 supplied is according
to the cell needs, ATP production fills the needs of the cell to make
the pumps to work and pH is established around 7.0. When hypoxia
occurs there is necrosis in some cells and in the penumbra involving
necrosis, the cells enter into a process of apoptosis where it will be
possible to rescue some of the cells that did not enter into the
necrosis processes.
How could we protect nerve cells from insults?
By this I mean to protect neurons from ischemia and/or hypoxia,
from trauma, from neurodegenerative diseases. What do all these
situations have in common? The answer is the death of neurons. So
the emergent question is how neurons are killed? Glutamate is now
accepted to be the main «killer» of neurons after brain insults.
Glutamate acts both as a primary excitatory neurotransmitter and a
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