Phosphorylation of the inositol 1,4,5-trisphosphate receptor. Cyclic GMP-dependent protein kinase mediates cAMP and cGMP dependent phosphorylation in the intact rat aorta.
The effects of cyclic GMP (cGMP) and activation of cGMP-dependent protein kinase (PKG) on the phosphorylation of the inositol 1,4, 5-trisphosphate (IP3) receptor were examined in intact rat aorta using the technique of back phosphorylation. Aorta treated with the nitric oxide donors, S-nitroso-N-acetylpenicillamine and sodium nitroprusside, or the selective PKG activator, 8-(4-para-chlorophenylthio)-cGMP (8-CPT-cGMP), demonstrated increased IP3 receptor phosphorylation in situ, which was both time- and concentration-dependent with a stoichiometry of 0.5 mol of phosphate/mol of receptor above control. Treatment of aorta with the adenyl cyclase activator, forskolin, also demonstrated increased phosphorylation of the IP3 receptor on the PKG site, although the selective cAMP-dependent protein kinase activator, 8-(4-para-chlorophenylthio)-cAMP (8-CPT-cAMP), did not increase the phosphorylation of the IP3 receptor. Moreover, the PKG selective inhibitor, KT 5823, inhibited both sodium nitroprusside and forskolin-induced IP3 receptor phosphorylation more potently than the selective cAMP-dependent protein kinase inhibitor, KT 5720, suggesting that PKG mediates the increase in IP3 receptor phosphorylation by both cyclic nucleotides in intact aorta. These results provide further support for the notion that PKG is activated by both cAMP and cGMP in intact vascular smooth muscle and that PKG performs a critical role in cyclic nucleotide-dependent relaxation of blood vessels.
Komalavilas
P
P
Department of Pathology, University of Alabama at Birmingham, 35294-0019, USA.
Lincoln
T M
TM
D000470:Alkaloids / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology*; D015220:Calcium Channels / Q000378:metabolism*; D002227:Carbazoles; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D007211:Indoles / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010766:Phosphorylation; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
D000470:Alkaloids; D015220:Calcium Channels; D002227:Carbazoles; D007211:Indoles; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011758:Pyrroles; D018160:Receptors, Cytoplasmic and Nuclear; D013873:Thionucleotides; D000804:Angiotensin II; C073601:KT 5823; D009599:Nitroprusside; D005576:Colforsin; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; C057416:KT 5720; D000242:Cyclic AMP; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP