Document Detail

MT2 receptors mediate the inhibitory effects of melatonin on nitric oxide-induced relaxation of porcine isolated coronary arteries.
MedLine Citation:
PMID:  20959363     Owner:  NLM     Status:  MEDLINE    
Previous studies from our laboratory demonstrated that melatonin inhibits nitric oxide (NO)-induced relaxation in porcine coronary arteries. The present study was designed to further characterize the mechanisms underlying this inhibitory effect of melatonin. Western immunoblot studies identified the presence of melatonin type 2 (MT(2)) receptors, but not MT(1) or MT(3) receptors, in porcine coronary arteries. Immunohistochemical analysis revealed that MT(2) receptors colocalized with α-actin in the smooth muscle cell layer. In coronary arterial rings suspended in organ chambers for isometric tension recording, melatonin (10(-7) M) inhibited relaxations induced by the exogenous NO donor sodium nitroprusside (SNP; 10(-9) to 10(-5) M) and by the α(2)-adrenoceptor agonist 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline (UK14,304; 10(-9) to 10(-5) M), an endothelium-dependent vasodilator. The inhibitory effect of melatonin on SNP- and UK14,304-induced relaxations was abolished in the presence of the selective MT(2) receptor antagonists 4-phenyl-2-propionamidotetralin (4P-PDOT; 10(-7) M) and luzindole (10(-7) M). In contrast to melatonin, the selective MT(3) receptor agonist 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT; 10(-7) M) had no effect on the concentration-response curves to either SNP or UK14,304. Melatonin (10(-7) M) had no effect on coronary artery relaxation induced by 8-bromoguanosine 3',5'-cyclic monophosphate, but it significantly attenuated the increase in intracellular cyclic GMP levels in response to SNP (10(-5) M). This effect of melatonin was abolished in the presence of 4P-PDOT (10(-7) M). Taken together, these data support the view that melatonin acts on MT(2) receptors in coronary vascular smooth muscle cells to inhibit NO-induced increases in cyclic GMP and coronary arterial relaxation, thus demonstrating a novel function for MT(2) receptors in the vasculature.
Radhika R Tunstall; Praveen Shukla; Anna Grazul-Bilska; Chengwen Sun; Stephen T O'Rourke
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-19
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  336     ISSN:  1521-0103     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-16     Completed Date:  2011-01-18     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  127-33     Citation Subset:  IM    
Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108-6050, USA.
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MeSH Terms
Coronary Vessels / metabolism*,  physiology
Melatonin / pharmacology,  physiology*
Muscle, Smooth, Vascular / cytology,  metabolism
Nitric Oxide / antagonists & inhibitors*,  physiology*
Nitric Oxide Donors / pharmacology
Receptor, Melatonin, MT2 / physiology*
Vasodilation / drug effects,  physiology*
Grant Support
Reg. No./Substance:
0/Nitric Oxide Donors; 0/Receptor, Melatonin, MT2; 10102-43-9/Nitric Oxide; 73-31-4/Melatonin

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