Cyclic AMP generating system in human microvascular endothelium is highly responsive to adrenaline

• Published in: Pharmacological reports Vol. 58; no. 6; pp. 884 - 889
• Main Authors: Namiecinska, Magdalena, Wiktorowska-Owczarek, Anna, Loboda, Agnieszka, Dulak, Józef, Nowak, Jerzy Z
• Format: Journal Article
• Language: English
• Published: Switzerland 01.11.2006
• Subjects: 1-Methyl-3-isobutylxanthine - pharmacology; Cells, Cultured; Cyclic AMP - biosynthesis; Endothelial Cells - metabolism; Epinephrine - pharmacology; Humans; Interleukin-8 - genetics; Isoproterenol - pharmacology; Signal Transduction - drug effects; Vascular Endothelial Growth Factor A - genetics
• ISSN: 1734-1140

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.