The direct stimulation of Gi proteins by neuropeptide Y (NPY) in the rat left ventricle.
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 Gialpha 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.
Raimondi
Laura
L
Department of Pharmacology, University of Florence, Florence, Italy. raimondi@server1.pharm.unifi.it
Banchelli
Grazia
G
Matucci
Rosanna
R
Stillitano
Francesca
F
Pirisino
Renato
R
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000276:immunology / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006868:Hydrolysis; D007700:Kinetics; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects
D000906:Antibodies; C092926:BIBP 3226; D009478:Neuropeptide Y; D005576:Colforsin; D006160:Guanosine Triphosphate; D001120:Arginine; D000242:Cyclic AMP; D020558:GTP Phosphohydrolases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go