Download physiological role of neuropeptide y in sympathetic neurotransmission

PHYSIOLOGICAL ROLE OF NEUROPEPTIDE Y IN SYMPATHETIC
NEUROTRANSMISSION
Thomas C. Westfall, Heather Macarthur, Chun-Lian Yang, Alice Gardner and
Linda Naes
Department of Pharmacological and Physiological Science, Saint Louis
University, USA
Sympathetic neurons, especially those innervating the vasculature are known
to contain neuropeptide Y (NPY), norepinephrine (NE) and adenosine
triphosphate (ATP) which can act as cotransmitters. NPY has been shown to
exert prejunctional inhibitory effects on transmitter release as well as
postjunctional contractile effects. We have previously obtained evidence that
the effect of NPY exerts a functional role in the modulation of sympathetic
transmitter release and the present study provides further support for this idea.
We investigated the prejunctional effects of NPY agonists and antagonists on
the nerve stimulation induced release of NE and NPY-ir from the perfused
mesenteric arterial bed of the rat.
The effect of selective NPY agonists and antagonists on the evoked release of
NE and NPY-ir were determined. Y2 agonists were shown to inhibit the evoked
release of NE and this was attenuated by theY2 antagonist BIIE0246. The Y2
agonists all had their greatest inhibitory effect at low frequencies of nerve
stimulation and the inhibitory effect was lost at high frequencies of nerve
stimulation. In contrast the Y2 antagonist BIIE0246 enhanced the nerve
stimulation induced overflow of NE and the increase was greatest at the higher
frequency of nerve stimulation. The Y2 agonists not only inhibited the evoked
release of NE but also the nerve stimulation induced increase in perfusion
pressure. In contrast Y1 selective agonists facilitated the increase in perfusion
pressure. In contrast to the prejunctional inhibitory effect of NPY13-36 on the
evoked release of NE, it enhanced the stimulation induced release of NPY-ir.
Like the inhibitory effect, the facilitation was greatest at low frequencies nerve
stimulation and lost as the frequency increased. Together these results are
consistent with NPY exerting physiological regulation of neurotransmitter
release from sympathetic neurons via Y2 receptors.
(Supported by NSPHS grant HL60260)