Different patterns of protein kinase C redistribution mediated by alpha 1-adrenoceptor stimulation and phorbol ester in rat isolated left ventricular papillary muscle.
1. In rat left ventricular papillary muscle, phenylephrine, an alpha 1-adrenoceptor agonist, had a staurosporine-sensitive positive inotropic effect and increased the particulate-associated protein kinase C (PKC) activity without significant changes in total PKC activity or in cytosolic Ca2+/phospholipid-independent kinase (PKI) activity. 2. A PKC stimulant, phorbol 12,13-dibutyrate (PDBu), decreased contractility and slightly increased PKC activity in the particulate fractions, with a marked decrease and increase in total PKC and PKI activities, respectively. 3. The PDBu-induced negative inotropic response was attenuated by two protease inhibitors, leupeptine and a microbial peptide isolated from Aspergillus japonicus (E-64), which are known to inhibit the conversion of particulate-associated PKC to PKI. 4. Such differences in the patterns of PKC redistribution, i.e. marked increases in particulate PKC and cytosolic PKI activities caused by phenylephrine and PDBu, respectively, may account for the opposite inotropic effects of PKC stimulation by an alpha 1-agonist and a phorbol ester.
Department of Pharmacology, Kansai Medical University, Osaka, Japan.
H
H
Otani
M
M
Hara
X T
XT
Zeng
K
K
Omori
C
C
Inagaki
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects / Q000201:enzymology*; D010656:Phenylephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D007976:Leupeptins; D011480:Protease Inhibitors; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D007930:Leucine; C032854:leupeptin; C024974:E 64