Regulation of phosphoinositide turnover in endothelium from human pulmonary artery, aorta and umbilical vein. Antagonistic action on the beta-adrenoceptor coupled adenylate cyclase system.
Ca2+-mobilizing receptor-induced inositol phospholipid hydrolysis has been studied in cultured endothelial cells (EC) from human aorta, pulmonary artery, and umbilical vein. It was shown that in EC the release of inositol phosphates can be stimulated by histamine, thrombin, serotonin, acetylcholine, carbachol, bradykinin, vasopressin, angiotensin II, platelet-activating factor (PAF), the thromboxane A2 mimetic, U46619, and prostaglandin E2. The most effective agonists were thrombin, histamine, and PAF, producing two- to five-fold increases in inositol phosphate level, and a 50-90% elevation of the level of inositol trisphosphate within 5 min. Effects of other agonists were smaller, although significant. Incubation of EC with histamine or PAF for 1 h resulted in a four- to eight-fold decrease of beta-adrenoreceptor density in the plasma membranes. The activity of isoproterenol-stimulated adenylate cyclase was depressed, and the degree of stimulation by isoproterenol was reduced. Similar effects were obtained after treatment of EC with the protein kinase C activator 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, suggesting a role of protein kinase C in receptor desensitization. It is concluded, that stimulation of inositol phospholipid hydrolysis, and, consequently, activation of protein kinase can cause receptor imbalance in human vascular endothelium. This mechanism may play a pivotal role in the pathogenesis of cardiovascular and pulmonary diseases.
Grigorian
G Y
GY
Institute of Experimental Cardiology, Academy of Medical Sciences, Moscow, USSR.
Mirzapoyazova
T Y
TY
Resink
T J
TJ
Danilov
S M
SM
Tkachuk
V A
VA
D000262:Adenylyl Cyclases / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D010716:Phosphatidylinositols / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology
D010716:Phosphatidylinositols; D010972:Platelet Activating Factor; D011943:Receptors, Adrenergic, beta; D006632:Histamine; D011493:Protein Kinase C; D013917:Thrombin; D000262:Adenylyl Cyclases