Cyclic AMP generating system in human microvascular endothelium is highly responsive to adrenaline.
We have tested cultured human microvascular endothelial cells (HMEC-1) for their ability to synthesize cyclic adenosine 3',5'-monophosphate (cAMP) in the absence or presence of various drugs. The accumulation of cAMP was only slightly affected by the addition of a phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) to the incubation medium. A direct stimulator of adenylyl cyclase forskolin and adrenergic drugs, such as adrenaline and noradrenaline, strongly increased cAMP accumulation in IBMX-treated HMEC-1 cells, whereas some other drugs known to stimulate the nucleotide synthesis in different cell/tissues were inactive (dopamine, histamine). Adrenaline was significantly more potent than noradrenaline. The effect of adrenaline on cyclic AMP production was reproduced by a selective beta-adrenoceptor agonist isoprenaline, antagonized by beta-blocker propranolol, and was not influenced by both alpha(1) and alpha(2)-selective antagonists, prazosin and yohimbine, respectively. Adrenaline did not significantly affect the ability of HMEC-1 cells to produce vascular endothelial growth factor (VEGF) or interleukin-8 (IL-8), the major angiogenic mediators. The results indicate that under basal (non-stimulated) conditions, the cAMP generating system of HMEC-1 cells maintained in culture remains rather quiescent, yet it can strongly respond to the hormone adrenaline acting on beta-adrenergic receptors.
Namiecinska
Magdalena
M
Center of Medical Biology, Polish Academy of Sciences, Lodowa 106, PL 93-232 Łódź, Poland.
Wiktorowska-Owczarek
Anna
A
Loboda
Agnieszka
A
Dulak
Józef
J
Nowak
Jerzy Z
JZ
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis*; D042783:Endothelial Cells / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D007545:Isoproterenol / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D016209:Interleukin-8; D042461:Vascular Endothelial Growth Factor A; D000242:Cyclic AMP; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine; D004837:Epinephrine