2-Chloroadenosine prevents phorbol ester-induced depletion of protein kinase C in porcine coronary artery. 1993

R B Marala, and K Ways, and S J Mustafa
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858.

In this study we investigated the role of the adenosine analogue 2-chloroadenosine (CAD) in the regulation of protein kinase C (PKC) in porcine coronary artery. Arterial rings were contracted with endothelin-1 (ET-1; 10(-10) to 10(-7) M) and phorbol 12,13-dibutyrate (PDBu; 10(-7) M) after incubating them for 1 and 2 days with PDBu (200 nM) in the presence and absence of CAD (10(-4) M). Chronic exposure to PDBu alone attenuated ET-1-induced contractions, while inclusion of CAD during incubation protected against the PDBu-induced blunting of ET-1-induced contraction. Similarly, PDBu (10(-7) M)-induced contraction of the arterial rings was attenuated upon chronic incubation with PDBu, and once again, inclusion of CAD showed an improved response to PDBu-induced contraction when compared with PDBu alone. Incubation with PDBu (200 nM) for 20 min caused the PKC translocation from cytosol to membrane, whereas CAD totally blocked this translocation. Chronic (1 and 2 days) incubation with PDBu caused a substantial depletion of PKC activities in cytosol and membrane. The presence of CAD protected the PDBu-induced depletion of PKC in both cytosol and membrane. To replete PKC, after incubation with the drugs, the arteries were incubated in the absence of drugs for another 2 days. Arteries incubated with PDBu in the presence and absence of CAD recovered significantly in their response to ET-1 as well as PDBu. These results indicate that CAD protects against the PDBu-induced activation and depletion of PKC in porcine coronary artery.

UI MeSH Term Description Entries
D008297 Male Males
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D003331 Coronary Vessels The veins and arteries of the HEART. Coronary Arteries,Sinus Node Artery,Coronary Veins,Arteries, Coronary,Arteries, Sinus Node,Artery, Coronary,Artery, Sinus Node,Coronary Artery,Coronary Vein,Coronary Vessel,Sinus Node Arteries,Vein, Coronary,Veins, Coronary,Vessel, Coronary,Vessels, Coronary
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D014661 Vasoconstriction The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE. Vasoconstrictions
D015240 Phorbol 12,13-Dibutyrate A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems. Phorbol-12,13-Dibutyrate,12,13-Dibutyrate, Phorbol,Phorbol 12,13 Dibutyrate
D015762 2-Chloroadenosine 2-Chloroadenosine. A metabolically stable analog of adenosine which acts as an adenosine receptor agonist. The compound has a potent effect on the peripheral and central nervous system. 2 Chloroadenosine
D016232 Endothelins 21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides. Endothelium-Derived Vasoconstrictor Factors,Endothelin,Vasoconstrictor Factors, Endothelium-Derived

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