Regulation of protein kinase C after stimulation of alpha 1-adrenoceptors in rat hippocampus.
Endogenous inhibitor of protein kinases (type II inhibitor, GABA-modulin) blocks the phosphorylation catalyzed by cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) as a competitive inhibitor of substrate proteins when histone is used as a substrate. Moreover, type II inhibitor blocks the phosphorylation of endogenous membrane proteins by PKC. Stimulation of alpha 1-adrenoceptors induced rapid redistribution of PKC from cytosol to membrane fraction which lasted at least 3 h, accompanied by rapid and short-lasting translocation of type II inhibitor from membrane to cytosol fraction. The cytosol content of type II inhibitor reached maximal level 10 and 20 min and became normal again 40 min after i.p. administration of methoxamine. The above actions of methoxamine were completely blocked by pretreatment with prazosin. It seems that short-lasting redistribution of type II inhibitor from membrane to cytosol fraction allows the effective phosphorylation of membrane proteins by PKC after stimulation of alpha 1-adrenoceptors.
Department of Pharmacodynamics, Medical University of Lodz, Poland.
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Szmigielski
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Gorska
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D006657:Histones / Q000378:metabolism; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D010766:Phosphorylation; D011224:Prazosin / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D051381:Rats; D017208:Rats, Wistar
D000316:Adrenergic alpha-Agonists; D002352:Carrier Proteins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; C015482:protein kinase modulator; D000242:Cyclic AMP; D011493:Protein Kinase C; D008729:Methoxamine; D011224:Prazosin