Cyclic AMP generating system in human microvascular endothelium is highly responsive to adrenaline.
Journal Title: Pharmacological Reports - Year 2006, Vol 58, Issue 6
Abstract
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 cAMPwas only slightly affected by the addition of a phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) to the incubation medium. Adirect 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 AMPproduction 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.
Authors and Affiliations
Magdalena Namiecinska, Anna Wiktorowska-Owczarek, Agnieszka Loboda, Józef Dulak, Jerzy Nowak
Keywords
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