title: Prolactin-releasing peptide regulates cardiac contractility.
abstract: High levels of specific prolactin-releasing peptide (PrRP) binding sites have been found in the myocardium; however, the functional importance of PrRP in the regulation of cardiac function is unknown. In isolated perfused rat hearts, infusion of PrRP (1-100 nM) induced a dose-dependent positive inotropic effect. Inhibition of cAMP catabolism by IBMX, a phosphodiesterase inhibitor, failed to augment the contractile effect of PrRP. The protein phosphatase (PP1/PP2A) inhibitor calyculin A increased the inotropic response to PrRP, whereas the PP2A inhibitor okadaic acid had no effect. Ro32-0432, a protein kinase C alpha (PKC alpha) inhibitor, significantly enhanced the inotropic effect of PrRP as well as the phosphorylation of phospholamban at Ser-16. In conclusion, the present data define a hitherto unrecognized role for PrRP in the regulation of cardiovascular system by showing that PrRP exerts a direct positive inotropic effect. Moreover, our results suggest that the cAMP-independent inotropic response to PrRP is suppressed by concurrent activation of PKC alpha and PP1.
authors.affiliation: Heart Institute, Medical School, University of Pécs, Pécs, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Kónyi
authors.forename: Réka
authors.initials: R
authors.lastname: Skoumal
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Kubin
authors.forename: Gábor
authors.initials: G
authors.lastname: Füredi
authors.forename: Abel
authors.initials: A
authors.lastname: Perjés
authors.forename: Klára
authors.initials: K
authors.lastname: Farkasfalvi
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Sárszegi
authors.forename: Ferenc
authors.initials: F
authors.lastname: Horkay
authors.forename: Iván G
authors.initials: IG
authors.lastname: Horváth
authors.forename: Miklós
authors.initials: M
authors.lastname: Tóth
authors.forename: Heikki
authors.initials: H
authors.lastname: Ruskoaho
authors.forename: István
authors.initials: I
authors.lastname: Szokodi
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D056690:Prolactin-Releasing Hormone / Q000494:pharmacology*; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D056690:Prolactin-Releasing Hormone; D051571:Protein Kinase C-alpha; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2