Synergistic potentiation of polyphosphoinositide breakdown by adenylate cyclase coupled receptors in human endothelial cells.
Histamine induces dose-dependent increases in inositol-monophosphate, inositol-bisphosphate, and inositol-triphosphate in cultured human pulmonary artery and umbilical vein endothelial cells. Preincubation with isoproterenol results in synergistic potentiation of polyphosphoinositide breakdown. Isoproterenol does not change the effect of histamine, however, it does increase the potency of histamine in stimulating phosphoinositide turnover. This effect of isoproterenol is time-dependent reaching 350% at 120 min of preincubation. A synergistic potentiation of histamine-induced polyphosphoinositide breakdown by cyclic AMP stimulators has been observed after pretreatment of cultured endothelial cells with forskolin, dibutyryl cyclic AMP and cholera toxin. Our data suggest that isoproterenol potentiates histamine-induced polyphosphoinositide breakdown by operating via the adenylate cyclase system. This is the first evidence of synergistic potentiation of polyphosphoinositide breakdown by adenylate cyclase-coupled receptors in cultured human endothial cells.
Voino-Yasenetskaya
T A
TA
Institute of Experimental Cardiology, Academy of Medical Sciences, Moscow, USSR.
Grigorian
G Y
GY
Danilov
S M
SM
Resink
T J
TJ
Tkachuk
V A
VA
Repin
V S
VS
D000262:Adenylyl Cyclases / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011953:Receptors, Cyclic AMP / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction
D010716:Phosphatidylinositols; D011953:Receptors, Cyclic AMP; D005576:Colforsin; D003994:Bucladesine; D006632:Histamine; D002772:Cholera Toxin; D000262:Adenylyl Cyclases; D007545:Isoproterenol