Biomaterial Database

Endothelin secretion is regulated by cyclic AMP and phosphatase 2A in endothelial cells. 1994

A Magnusson, and H Halldorsson, and G Thorgeirsson, and M Kjeld

Department of Pharmacology, University of Iceland, Reykjavik.

Endothelin is a 21 amino acid peptide secreted by endothelial cells and is the most potent vasoconstrictor known. The present study examines regulatory mechanisms of endothelin secretion, focusing on the role of protein phosphorylation. Endothelin secretion was measured by radioimmunoassay in primary cultures of human umbilical vein endothelial cells. While treatment that raised cAMP levels reduced the basal endothelin secretion rate, agents that elevated cGMP had no effect. Downregulation or inhibition of protein kinase C resulted in decreased endothelin secretion, suggesting that protein kinase C regulates endothelin secretion in the opposite direction to cAMP dependent protein kinases. Okadaic acid, at concentrations that selectively inhibit protein phosphatases 2A, reduced the endothelin secretion and the effects of okadaic acid and db-cAMP were additive. Endothelin production was stimulated by fetal calf serum and by the protein kinase inhibitor 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H7), but was inhibited by the calmodulin antagonist trifluoperazine. The present findings that regulators of cAMP-dependent protein kinases, protein kinase C, calmodulin, and protein phosphatase 2A all affect endothelin secretion suggest that endothelin secretion is controlled by phosphorylation/dephosphorylation of as yet unidentified regulatory proteins within the cell.

UI	MeSH Term	Description	Entries
D010749	Phosphoprotein Phosphatases	A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)	Phosphoprotein Phosphatase,Phosphoprotein Phosphohydrolase,Protein Phosphatase,Protein Phosphatases,Casein Phosphatase,Ecto-Phosphoprotein Phosphatase,Nuclear Protein Phosphatase,Phosphohistone Phosphatase,Phosphoprotein Phosphatase-2C,Phosphoseryl-Protein Phosphatase,Protein Phosphatase C,Protein Phosphatase C-I,Protein Phosphatase C-II,Protein Phosphatase H-II,Protein-Serine-Threonine Phosphatase,Protein-Threonine Phosphatase,Serine-Threonine Phosphatase,Threonine Phosphatase,Ecto Phosphoprotein Phosphatase,Phosphatase C, Protein,Phosphatase C-I, Protein,Phosphatase C-II, Protein,Phosphatase H-II, Protein,Phosphatase, Casein,Phosphatase, Ecto-Phosphoprotein,Phosphatase, Nuclear Protein,Phosphatase, Phosphohistone,Phosphatase, Phosphoprotein,Phosphatase, Phosphoseryl-Protein,Phosphatase, Protein,Phosphatase, Protein-Serine-Threonine,Phosphatase, Protein-Threonine,Phosphatase, Serine-Threonine,Phosphatase, Threonine,Phosphatase-2C, Phosphoprotein,Phosphatases, Phosphoprotein,Phosphatases, Protein,Phosphohydrolase, Phosphoprotein,Phosphoprotein Phosphatase 2C,Phosphoseryl Protein Phosphatase,Protein Phosphatase C I,Protein Phosphatase C II,Protein Phosphatase H II,Protein Phosphatase, Nuclear,Protein Serine Threonine Phosphatase,Protein Threonine Phosphatase,Serine Threonine Phosphatase
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004730	Endothelium, Vascular	Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.	Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D004988	Ethers, Cyclic	Compounds of the general formula R-O-R arranged in a ring or crown formation.	Cyclic Ether,Cyclic Ethers,Ether, Cyclic
D005576	Colforsin	Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.	Coleonol,Forskolin,N,N-Dimethyl-beta-alanine-5-(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho(2,1-b)pyran-6-yl Ester HCl,NKH 477,NKH-477,NKH477
D006152	Cyclic GMP	Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)	Guanosine Cyclic 3',5'-Monophosphate,Guanosine Cyclic 3,5 Monophosphate,Guanosine Cyclic Monophosphate,Guanosine Cyclic-3',5'-Monophosphate,3',5'-Monophosphate, Guanosine Cyclic,Cyclic 3',5'-Monophosphate, Guanosine,Cyclic Monophosphate, Guanosine,Cyclic-3',5'-Monophosphate, Guanosine,GMP, Cyclic,Guanosine Cyclic 3',5' Monophosphate,Monophosphate, Guanosine Cyclic
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000242	Cyclic AMP	An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.	Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D015056	1-Methyl-3-isobutylxanthine	A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASES	3-Isobutyl-1-methylxanthine,Isobutyltheophylline,IBMX,1 Methyl 3 isobutylxanthine,3 Isobutyl 1 methylxanthine
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