Prolactin-releasing peptide regulates cardiac contractility.
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.
Kónyi
Attila
A
Heart Institute, Medical School, University of Pécs, Pécs, Hungary.
Skoumal
Réka
R
Kubin
Anna-Maria
AM
Füredi
Gábor
G
Perjés
Abel
A
Farkasfalvi
Klára
K
Sárszegi
Zsolt
Z
Horkay
Ferenc
F
Horváth
Iván G
IG
Tóth
Miklós
M
Ruskoaho
Heikki
H
Szokodi
István
I
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
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D056690:Prolactin-Releasing Hormone; D051571:Protein Kinase C-alpha; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2