Characteristics of adrenaline-driven receptor-mediated signals in human microvessel-derived endothelial cells

• Published in: Pharmacological reports Vol. 60; no. 6; pp. 950 - 956
• Main Authors: Wiktorowska-Owczarek, Anna, Namiecińska, Magdalena, Berezińska, Małgorzata, Nowak, Jerzy Z
• Format: Journal Article
• Language: English
• Published: Switzerland 01.11.2008
• Subjects: Cells, Cultured; Cyclic AMP - biosynthesis; Cyclic Nucleotide Phosphodiesterases, Type 4 - physiology; Endothelial Cells - metabolism; Epinephrine - pharmacology; Humans; Microvessels - cytology; Propranolol - pharmacology; Receptors, Adrenergic, alpha - physiology; Receptors, Adrenergic, beta - physiology; Signal Transduction
• ISSN: 1734-1140

Adrenaline (0.001-1,000 muM) strongly stimulated adenosine-3',5'cyclic monophosphate (cAMP) generation in cultured human microvascular-derived endothelial cells (HMEC-1). Isoprenaline mimicked the action of adrenaline, whereas noradrenaline appeared to be decisively less potent. Experiments carried out with an array of compounds acting selectively on different types/subtypes of adrenergic receptors revealed that the adrenaline cAMP effect in HMEC-1 cells did not possess either an alpha(1) or alpha(2) component. However, the effect may have been mediated through a receptor that did not fit beta(1)-, beta(2)-, or beta(3)-receptor classification. Supporting this assertion, various double and triple beta-subtype selective drug combinations maximally inhibited the adrenaline effect by 50-60%, whereas the non-selective antagonist propranolol totally prevented the hormone-evoked cAMP effect. Based on results utilizing the phosphodiesterase (PDE)-isoform nonselective inhibitor 3-isobutyl-1-methylxanthine (IBMX) and the PDE-4-selective inhibitor rolipram, the adrenaline-driven cAMP signal appeared to be regulated by PDE-4. In addition, the present study demonstrated that phenylephrine, a presumed selective alpha(1)-adrenoceptor agonist, was capable of stimulating cAMP generation in HMEC-1 cells in a prazosin-insensitive and propranolol-sensitive manner. This result indicated that in at least this cell model system, phenylephrine may act nonspecifically. Microvessel-derived endothelial cells such as HMEC-1 exhibit functional differences when compared with macrovessel-derived endothelial cells (e.g. HUVEC sensitivity to adrenaline). Accordingly, these cell cultures represent a useful model system to study the biological effects of endogenous catecholamines, including adrenaline, as well as potential therapeutics targeting adrenergic receptors.