TY - JOUR
T1 - The direct stimulation of Gi proteins by neuropeptide Y (NPY) in the rat left ventricle
AU - Raimondi, Laura
AU - Banchelli, Grazia
AU - Matucci, Rosanna
AU - Stillitano, Francesca
AU - Pirisino, Renato
PY - 2002/6/1
Y1 - 2002/6/1
N2 - Neuropeptide Y (NPY) is a neuropeptide with high distribution in the cardiovascular system of mammals, where it modulates heart and vessel contractility. In the rat heart, the presence of at least three different NPY receptor subtypes has been hypothesised. Notwithstanding this, receptor activation might not be the only mechanism responsible for the complex cardiac effects of the peptide. In this study, we investigated the effect of NPY on the GTPase activity of G-proteins in the rat left ventricle as a possible alternative mechanism of action for the peptide in the rat heart. Our results show that NPY, but also the neuropeptide fragment (18-36) (NPY (18-36)), stimulated the basal, spontaneous GTPase activity of ventricle membranes only when it was measured under the condition of an absence of Mg2+. This stimulation was resistant to BIBP3226 a non-peptidergic antagonist at Y1 receptors, but it was significantly reduced in membranes treated with selective antibodies against the Giα subunits. NPYs effect was concentration-dependent with a maximum of activity at 10nM. At this concentration, NPY (and NPY 18-36) was able to inhibit forskolin (FSK)-induced cyclic adenosine-5′-monophosphate (cAMP) elevation in rat left ventricle slices. Our results assess that NPY in the rat heart is able to activate the GTPase activity of Gi proteins, in a receptor-independent way.
AB - Neuropeptide Y (NPY) is a neuropeptide with high distribution in the cardiovascular system of mammals, where it modulates heart and vessel contractility. In the rat heart, the presence of at least three different NPY receptor subtypes has been hypothesised. Notwithstanding this, receptor activation might not be the only mechanism responsible for the complex cardiac effects of the peptide. In this study, we investigated the effect of NPY on the GTPase activity of G-proteins in the rat left ventricle as a possible alternative mechanism of action for the peptide in the rat heart. Our results show that NPY, but also the neuropeptide fragment (18-36) (NPY (18-36)), stimulated the basal, spontaneous GTPase activity of ventricle membranes only when it was measured under the condition of an absence of Mg2+. This stimulation was resistant to BIBP3226 a non-peptidergic antagonist at Y1 receptors, but it was significantly reduced in membranes treated with selective antibodies against the Giα subunits. NPYs effect was concentration-dependent with a maximum of activity at 10nM. At this concentration, NPY (and NPY 18-36) was able to inhibit forskolin (FSK)-induced cyclic adenosine-5′-monophosphate (cAMP) elevation in rat left ventricle slices. Our results assess that NPY in the rat heart is able to activate the GTPase activity of Gi proteins, in a receptor-independent way.
KW - G-proteins
KW - Heart metabolism
KW - Second messengers
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=0036609290&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(02)00986-3
DO - 10.1016/S0006-2952(02)00986-3
M3 - Article
C2 - 12093484
AN - SCOPUS:0036609290
SN - 0006-2952
VL - 63
SP - 2063
EP - 2068
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 11
ER -