QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.102103v1 318/1/336    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Angelone, T. Articles by Tota, B. Search for Related Content PubMed PubMed Citation Articles by Angelone, T. Articles by Tota, B.

CARDIOVASCULAR

The Emerging Cardioinhibitory Role of the Hippocampal Cholinergic Neurostimulating Peptide

Departments of Pharmaco-Biology (T.A., M.C.C.) and Cell Biology (T.A., M.C.C., B.T.), University of Calabria, Arcavacata di Rende, Italy; and Institut National de la Santé et de la Recherche Médicale U575 Physiopatologie du Système Nerveux, Strasbourg, France (Y.G., M.-H.M.-B., D.A., T.A.)

Hippocampal cholinergic neurostimulating peptide (HCNP), which derives from phosphatidylethanolamine-binding protein (also named Raf kinase inhibitor protein), enhances acetylcholine synthesis in the hippocampal medial septal nuclei. It is present in the chromaffin secretory granules of the adrenal cells and under stress is cosecreted with peptide hormones and catecholamines. Using the isolated rat heart perfused according to Langendorff to reveal the cardiotropic action of HCNP on the mammalian heart, we showed that rat HCNP exerts, at concentrations of 5 x 10^-13 to 10^-6 M, a negative inotropism under basal conditions (left ventricular pressure variations ranging from -8.34 ± 0.94% to -21 ± 3.5%) and enhances the cholinergic-mediated negative inotropy through direct interaction with G-protein-coupled muscarinic receptor pathway. Under adrenergic stimulation (isoproterenol), the peptide exerts an antiadrenergic action. The analysis of the percentage of rate pressure product variations in terms of EC₅₀ values of isoproterenol alone (-8.5 ± 0.3; r² = 0.90) and in the presence of rat HCNP at 0.01 nM (-6.9 ± 0.36; r² = 0.88) revealed a competitive type of antagonism of the peptide. HCNP does not affect either heart rate or coronary pressure. The evidence that HCNP in mammals may play a novel role as an inhibitory cardiac modulator throughout an involvement of the myocardial G-protein-coupled receptor pathway provides new insights regarding the neurohumoral control of heart function under normal and physiopathological conditions.

Address correspondence to: Dr. Bruno Tota, Department of Cell Biology, University of Calabria, 87030 Arcavacata di Rende (CS), Italy. E-mail: tota{at}unical.it

This article has been cited by other articles:

				M. C. Cerra, M. P. Gallo, T. Angelone, A. M. Quintieri, E. Pulera, E. Filice, B. Guerold, P. Shooshtarizadeh, R. Levi, R. Ramella, et al. The homologous rat chromogranin A1-64 (rCGA1-64) modulates myocardial and coronary function in rat heart to counteract adrenergic stimulation indirectly via endothelium-derived nitric oxide FASEB J, November 1, 2008; 22(11): 3992 - 4004. [Abstract] [Full Text] [PDF]