Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-12-3
pubmed:abstractText
Our recent findings indicate that, in rat neonatal ventricular cardiomyocytes, endothelin-1 (ET-1) induces increases in the rate of protein synthesis in a partly pertussis toxin (PTX)-sensitive manner, and that angiotensin II-evoked increases in the rate of protein synthesis are brought about via local secretion of ET-1. The aim of this study was to find out: (1) whether noradrenaline (NA) and the thromboxane A2 (TXA2)-mimetic U 46619-induced increases in the rate of protein synthesis may be also partly PTX-sensitive and/or mediated by ET-1, and (2) whether the growth-promoting effects of NA and U 46619 as well as ET-1 might involve activation of the same set of protein kinase C (PKC) isozymes. For this purpose we first studied the effects of NA and U 46619 on inositol phosphate (IP)-formation (assessed as accumulation of total [3H]IPs in myo-[3H]inositol prelabelled cells) and on the rate of protein synthesis (assessed as [3H]phenylalanine incorporation) (1) in the presence and absence of the ET(A)-receptor antagonist BQ-123, and (2) in nontreated and PTX-pretreated cells. Second, we assessed the effects of the PKC-inhibitors bisindolylmaleimide I and Gö 6976 and of phorbol-12-myristate-13-acetate (PMA; 1 microM overnight)-pretreatment on U 46619-, NA- and ET-1-induced increases in the rate of protein synthesis. NA (0.01-10 microM) concentration-dependently increased IP-formation (maximum increase: 115-/+23% above basal, n=4) and [3H]phenylalanine incorporation (maximum increase: 40+/-3% above basal, n=20). Both responses were antagonized by the alpha1-adrenoceptor antagonist prazosin (1 microM), but were not significantly affected by BQ-123 (1 microM). U 46619 (0.01-100 microM) concentration-dependently increased IP-formation (maximum increase: 89+/-12% above basal, n=8) and [3H]phenylalanine incorporation (maximum increase: 33+/-4% above basal, n=16). Both responses were slightly but significantly antagonized by the TP-receptor antagonist SQ 29548 (1 microM), but were not affected by BQ-123 (1 microM). Pretreatment of the cardiomyocytes with 250 ng ml(-1) PTX overnight did not significantly affect NA- and U 46619-evoked increases in IP-formation and [3H]phenylalanine incorporation. The PKC-inhibitor bisindolylmaleimide I (5 microM) as well as pretreatment of the cells with PMA (1 microM) significantly reduced the effects of NA, U 46619 and ET- I on the rate of protein synthesis; in contrast, the PKC-inhibitor Gö 6976 (5 microM) was without any effects. We conclude that, in rat neonatal ventricular cardiomyocytes, stimulation of Gq/11-coupled receptors increases the rate of protein synthesis; this involves activation of the same PKC-isozymes (very likely PKC-delta and/or -epsilon). NA and U 46619 cause their growth-promoting effects in a PTX-insensitive manner; ET-1 is not involved in their effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/15-Hydroxy-11 alpha,9..., http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic alpha-Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Carbachol, http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha..., http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Hydrazines, http://linkedlifedata.com/resource/pubmed/chemical/Indoles, http://linkedlifedata.com/resource/pubmed/chemical/Inositol Phosphates, http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes, http://linkedlifedata.com/resource/pubmed/chemical/Maleimides, http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine, http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin, http://linkedlifedata.com/resource/pubmed/chemical/Phenylalanine, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface, http://linkedlifedata.com/resource/pubmed/chemical/SQ 29548, http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate, http://linkedlifedata.com/resource/pubmed/chemical/Tritium, http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella, http://linkedlifedata.com/resource/pubmed/chemical/bisindolylmaleimide I
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0028-1298
pubmed:author
pubmed:issnType
Print
pubmed:volume
360
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
301-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10543432-15-Hydroxy-11 alpha,9..., pubmed-meshheading:10543432-Adrenergic alpha-Agonists, pubmed-meshheading:10543432-Animals, pubmed-meshheading:10543432-Animals, Newborn, pubmed-meshheading:10543432-Carbachol, pubmed-meshheading:10543432-Dose-Response Relationship, Drug, pubmed-meshheading:10543432-Endothelin-1, pubmed-meshheading:10543432-Enzyme Inhibitors, pubmed-meshheading:10543432-GTP-Binding Protein alpha Subunits, Gi-Go, pubmed-meshheading:10543432-GTP-Binding Proteins, pubmed-meshheading:10543432-Heart Ventricles, pubmed-meshheading:10543432-Hydrazines, pubmed-meshheading:10543432-Indoles, pubmed-meshheading:10543432-Inositol Phosphates, pubmed-meshheading:10543432-Isoenzymes, pubmed-meshheading:10543432-Maleimides, pubmed-meshheading:10543432-Norepinephrine, pubmed-meshheading:10543432-Pertussis Toxin, pubmed-meshheading:10543432-Phenylalanine, pubmed-meshheading:10543432-Protein Biosynthesis, pubmed-meshheading:10543432-Protein Kinase C, pubmed-meshheading:10543432-Proteins, pubmed-meshheading:10543432-Rats, pubmed-meshheading:10543432-Receptors, Cell Surface, pubmed-meshheading:10543432-Tetradecanoylphorbol Acetate, pubmed-meshheading:10543432-Tritium, pubmed-meshheading:10543432-Virulence Factors, Bordetella
pubmed:year
1999
pubmed:articleTitle
Gq/11-coupled receptors and protein synthesis in rat cardiomyocytes: role of Gi-proteins and protein kinase C-isozymes.
pubmed:affiliation
Institute of Pharmacology and Toxicology, Martin Luther University of Halle-Wittenberg, Halle, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't