Xiao-Ping Yang and Shigetoshi Chiba*
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto
390-8621, Japan
*ﾊTo whom correspondence should be addressed.
Abstract: The present study observed the effects of an activation
of neuropeptideﾊY (NPY)ﾊY1 receptors on adrenergic and purinergic
components of double-peaked vasoconstrictor responses to periarterial nerve
stimulation in the isolated, perfused canine splenic arteries. The results
showed that 3-30ﾊnM Leu31ﾊPro34ﾊneuropeptideﾊY (LP-NPY)
produced a dose-dependent potentiation of double-peaked vasoconstrictor
responses to trains of 30-s pulses at 1, 4 or 10ﾊHz of stimulation. The
potentiation of LP-NPY of the nerve-stimulated vasoconstrictions were completely
inhibited by subsequent blockade of a1-adrenoceptors
or Y1 receptors with 0.1ﾊmM prazosin
or with 1ﾊmM BIBPﾊ3226 ((R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-argininamide),
respectively. The remaining responses in the presence of LP-NPY and prazosin
were abolished by P2X receptor desensitization with 1ﾊmM
a,b-methylene ATP.
Moreover, 30ﾊnM LP-NPY failed to modify the vasoconstrictor responses to
nerve stimulation after treatment with prazosin. A subsequent administration
of a,b-methylene ATP
completely suppressed the remaining responses after prazosin and LP-NPY.
The vasoconstrictions induced by 0.003-1ﾊnmol noradrenaline and 0.003-1ﾊmmol
ATP were slightly, but not significantly enhanced by 30ﾊnM LP-NPY. The observations
indicated that activation of postjunctional NPYﾊY1 receptors
may have an important role in the modulation of adrenergic rather than purinergic
transmission of the sympathetic co-transmission.
Keywords: Leu31 Pro34 neuropeptide Y, NPY Y1
receptor antagonist, BIBP 3226,
Sympathetic nerve stimulation, Splenic artery