Neuropeptide Y rapidly enhances [Ca2+]i transients and Ca2+ sparks in adult rat ventricular myocytes through Y1 receptor and PLC activation.
Neuropeptide Y (NPY) is the most abundant peptide in the mammalian heart, but its cardiac actions are not fully understood. Here we investigate the effect of NPY in intracellular Ca2+ release, using isolated rat cardiac myocytes and confocal microscopy. Cardiac myocytes were field-stimulated at 1 Hz. The evoked [Ca2+]i transient was of higher amplitude and of faster decay in the presence of 100 nM NPY. Cell contraction was also increased by NPY. We analyzed the occurrence of Ca2+ sparks and their characteristics after NPY application. NPY significantly increased Ca2+ sparks frequency in quiescent cells. The Ca2+ spark amplitude was enhanced by NPY but the other characteristics of Ca2+ sparks were not significantly altered. Because cardiac myocytes express both Y1 and Y2 NPY receptors, we repeated the experiments in the presence of the receptor blockers, BIBP3226 and BIIE0246. We found that Y1 NPY receptor blockade completely inhibited NPY effects on [Ca2+]i transient. PTX-sensitive G-proteins and/or phospholypase C (PLC) have been invoked to mediate NPY effects in other cell types. We tested these two hypotheses. In PTX-treated myocytes NPY was still effective, which suggests that the observed NPY actions are not mediated by PTX-sensitive G-proteins. In contrast, the increase in [Ca2+]i transient by NPY was completely inhibited by the PLC inhibitor U73122. In conclusion, we find that NPY has a positive inotropic effect in isolated rat cardiac myocytes, which involves increase in Ca2+ release after activation of Y1 NPY receptor and subsequent stimulation of PLC.
Heredia
María del Puy
Mdel P
Institute of Pharmacology and Toxicology, CSIC-UCM, Madrid, Spain.
Delgado
Carmen
C
Pereira
Laetitia
L
Perrier
Romain
R
Richard
Sylvain
S
Vassort
Guy
G
Bénitah
Jean-Pierre
JP
Gómez
Ana María
AM
D000375:Aging / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D004789:Enzyme Activation; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009478:Neuropeptide Y / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D013552:Swine; D010738:Type C Phospholipases / Q000378:metabolism*
D009478:Neuropeptide Y; C066211:Npy1r protein, rat; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D010738:Type C Phospholipases; D002118:Calcium