Urotensin II stimulates high frequency-induced ANP secretion via PLC-PI 3K-PKC pathway.
Urotensin II (U-II) and its receptor are coexpressed in the heart and show various cardiovascular functions. However, the relationship between U-II and cardiac hormone atrial natriuretic peptide (ANP) is still unknown. The aim of the present study is to test whether U-II affects ANP secretion using in vitro perfusion experiments and in vivo studies. Human U-II (hU-II) (10(-11), 5x10(-11), 10(-10), 5x10(-10)M) stimulated ANP secretion from isolated perfused rat atria paced with high frequency (6.0Hz). However, atrial contractility and translocation of extracellular fluid (ECF) did not change. An increase in ANP secretion by rat U-II was similar to that by hU-II; however, urotensin-related peptide showed no significant effect on ANP secretion. Pretreatment with urotensin receptor antagonist and inhibitor for phospholipase C (PLC), phosphoinositide 3-kinase (PI3K), or protein kinase C (PKC) attenuated hU-II-induced ANP secretion from atria paced with high frequency, but an inhibitor for inositol triphosphate did not. Intravenous infusion of hU-II at a dose of 2.5microM for 20min increased plasma ANP level, along with increased heart rate and pulse pressure in anesthetized rats. Therefore, we suggest that U-II stimulates high stimulation frequency-induced ANP secretion partly through the urotensin receptor and the PLC/PI3K/PKC pathway.
Gao
Shan
S
Department of Physiology, Diabetic Research Center, Chonbuk National University Medical School, Jeonju, Republic of Korea.
Shah
Amin
A
Oh
Young Bin
YB
Park
Woo Hyun
WH
Kim
Suhn Hee
SH
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism*; D014579:Urotensins / Q000494:pharmacology*
D014579:Urotensins; D009320:Atrial Natriuretic Factor; C029677:urotensin II; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases