Noradrenaline-induced increase in protein synthesis in adult rat cardiomyocytes: involvement of only alpha(1A)-adrenoceptors

Citation
K. Ponicke et al., Noradrenaline-induced increase in protein synthesis in adult rat cardiomyocytes: involvement of only alpha(1A)-adrenoceptors, N-S ARCH PH, 364(5), 2001, pp. 444-453
Citations number
44
Categorie Soggetti
Pharmacology & Toxicology
Journal title
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
ISSN journal
00281298 → ACNP
Volume
364
Issue
5
Year of publication
2001
Pages
444 - 453
Database
ISI
SICI code
0028-1298(200111)364:5<444:NIIPSI>2.0.ZU;2-X
Abstract
Adult rat ventricular cardiomyocytes, contain alpha (1A)- and alpha (1B)-ad renoceptors (ARs, 20%:80%, assessed by [H-3]prazosin binding). We studied w hich alpha (1)-AR subtype mediates noradrenaline (NA)-induced increase in r ate of protein synthesis, and which, signalling pathway is. involved. NA (1 0(-9)-10(-4) M) concentration-dependently increased inositol phosphate (T) formation (pEC(50)-value=6.1 +/-0.1, n=5) and protein synthesis (assessed a s [H-3]phenylalanine incorporation; pEC(50)-value=6.6 +/-0.1, n=6). NA-indu ced IP-formation was partly inhibited by the alpha (1B)-AR antagonist chlor oethylclonidine (CEC, 30 muM; 33 +/-9% inhibition, n=5); following CEC-trea tment the alpha (1A)-AR-selective 5-methyl-urapidil (5-MU) inhibited NA-ind uced IP-formation with a pK(i)-value of 9.2 +/-0.2 (n=6,); the alpha (1D)-A R-selective BMY 7378 was only a weak antagonist (pK(i)- value <7). NA-induc ed increase in protein synthesis, was insensitive to CEC whereas 5-MU inhib ited it with a pK(i)-value of 9.1 +/-0.2 (n=6). NA (1 muM)-induced increase in protein synthesis was inhibited by the protein kinase C (PKC) inhibitor bisindolylmaleimide (IC50-value: 206 nM), the PI 3-kinase inhibitors wortm annin (IC50 =3.4 nM) and LY 294002 (IC50=10 muM), and p70(s6)-kinase inhibi tor rapamycin (IC50=123 pM) but not by the p39 MAP-kinase inhibitor SB 2035 80: (10 muM) or the MEK-inhibitor PD 98059 (25 muM). Moreover, 5-MU (30 nM) but not CEC inhibited NA-induced activation of p70(s6)-kinase. We conclude that, in adult rat cardiomyocytes, alpha (1A)- and beta (1B)-AR mediate NA -induced IP-formation but only alpha (1A)-ARs mediate increase in protein s ynthesis. alpha (1A)-AR-mediated increase in protein synthesis involves act ivation of a PKC, PI 3-kinase and p70(s6)-kinase, but not of ERK- or p38 MA P-kinase.