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Phosphorylation of phospholamban correlates with relaxation of coronary artery induced by nitric oxide, adenosine, and prostacyclin in the pig
Author(s) -
Karczewski Peter,
Hendrischke Thomas,
Wolf WolfPeter,
Morano Ingo,
Bartel Sabine,
Schrader Jürgen
Publication year - 1998
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19980701)70:1<49::aid-jcb6>3.0.co;2-3
Subject(s) - phospholamban , prostacyclin , medicine , phosphorylation , endocrinology , adenosine , vascular smooth muscle , vasodilation , myosin light chain kinase , endothelium , chemistry , biology , biochemistry , smooth muscle
The intracellular mechanisms underlying the action of the endogenous vasodilators such as NO/EDRF, adenosine, and prostacyclin acting through cGMP and cAMP, respectively, are not well understood. One important action of cyclic nucleotides in smooth muscle relaxation is to lower the cytosolic Ca 2+ concentration by enhanced sequestration into the sarcoplasmic reticulum. The present study was undertaken to elucidate the potential role of phosphorylation of phospholamban, the regulator of sarcoplasmic reticulum Ca 2+ pump, for the control of coronary vascular tone by NO/EDRF, adenosine, and prostacyclin. Phospholamban was identified in pig coronary artery preparations by immunofluorescence microscopy, Western blotting and in vitro phosphorylation. Segments of pig coronary artery, with either intact or denuded endothelium, were precontracted with prostaglandin F 2 α (PGF 2 α ). In endothelium‐denuded preparations 3‐morpholinosydnonimine (SIN‐1), 5′‐N‐ethylcarboxiamidoadenosine (NECA), and iloprost (ILO) caused both relaxation and phospholamban phosphorylation with the potency: SIN‐1 > NECA > ILO. The regulatory myosin light chain was significantly dephosphorylated only by SIN‐1. In endothelium‐intact pig coronary artery, L‐NAME caused additional vasoconstriction and a decrease in phospholamban phosphorylation, while phosphorylation of myosin light chain remained unchanged. An inverse relationship between phospholamban phosphorylation and vessel tone was obtained. Our findings demonstrate significant phospholamban phosphorylation during coronary artery relaxation evoked by NO, prostacyclin, and adenosine receptor activation. Because of the close correlation between phosphorylation of phospholamban and vessel relaxation, we propose that phospholamban phosphorylation is an important mechanism by which endogenous vasodilators, especially endothelial NO/EDRF, control coronary vascular smooth muscle tone. J. Cell. Biochem. 70:49–59, 1998. © 1998 Wiley‐Liss, Inc.