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GEOFFREY BURNSTOCK AN. R. ACAD. NAC. FARM.

vasopressin via P1 receptors. Purinergic and adrenergic synergism
for vasopressin and oxytocin release is consistent with ATP
cotransmission in the hypothalamus. Purinergic signalling appears
to play a significant role in the regulation of body temperature during
fever by central hypothalamic and brainstem nuclei. Functional
interactions seem likely to occur between purinergic and nitrergic
neurotransmitter systems; they may be important for regulation of
hormone secretion and body temperature at the hypothalamic level
and for cardiovascular and respiratory control at the level of the
brainstem. ATP is coreleased with GABA or noradrenaline to act on
P2 receptors which are strongly expressed in most nuclei in the
hypothalamus, including arcuate, paraventricular, retrochiasmatic,
supraoptic, ventromedial and dorsomedial.

P2X and GABAA receptors play an important role in CO2
chemoreception and are involved in mediation of the ventilatory
response to hypercapnia. P2X receptors expressed in neurons in the
trigeminal mesencephalic nucleus may be involved in the processing
of proprioceptive information. The nucleus tractus solitarius (NTS)
is a major integrative centre in the brain stem involved in reflex
control of the cardiovascular system; stimulation of P2X receptors
in the NTS evokes hypotension with decrease in both cardiac
output and total peripheral resistance. Evaluation of the roles of
purinergic signalling in processing of the sympathoexcitatory
component of the chemoreflex at the NTS level may illuminate the
mechanisms underlying the sympathetic overactivity observed in
pathophysiological conditions such as hypertension, obstructive sleep
apnea and heart failure.

In the striatum, extracellular ATP and adenosine are involved in
the regulation of the feeding-associated mesolimbic neuronal activity
in an antagonistic manner. PPADS suppresses the feeding-evoked
dopamine release in the nucleus accumbens, a brain region regarded
as important for the regulation of appetite behaviour and
reinforcement. Adenosine-dopamine interactions in the ventral
striatum have been implicated in schizophrenia and A2A agonists
proposed as antipsychotics. A hypothesis has been put forward where
dysfunction of purinergic signalling (for example, decreased ATPase
activity in erythrocytes, leading to increased levels of ATP and
decreased adenosine) may lead to schizophrenia.

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