Beta-adrenergic receptors on human tracheal epithelial cells in primary culture

作者：Pamela B. Davis, Catherine L. Silski, Carolyn M. Kercsmar, Michael D. Infeld · 发表于：American Journal of Physiology-Cell Physiology · 年份：1990 · DOI：10.1152/ajpcell.1990.258.1.c71 · 被引用次数：62 · 研究领域：Asthma and respiratory diseases、Respiratory and Cough-Related Research、Ion channel regulation and function

Human tracheal epithelial cells in suspension, whether obtained by brushing at bronchoscopy or from necropsy specimens by proteolytic digestion and EDTA treatment, increase adenosine 3',5'-cyclic monophosphate (cAMP) production in response to isoproterenol. These cells in primary culture also respond to beta-adrenergic agonists in order of potency isoproterenol greater than epinephrine greater than norepinephrine. The response is inhibited by propranolol or ICI 118551 (a beta 2-adrenergic selective blocker) but not by atenolol (a beta 1-adrenergic blocker). Binding of [125I]iodocyanopindolol (ICYP) to membranes was rapid, stereoselective, and saturable and displayed receptor density 8.0 +/- 4.6 fmol/mg protein (mean 228 receptors/cell) and a dissociation constant (KD) for ICYP of 35 +/- 14 pM for freshly isolated cells and a KD of 25 +/- 13 pM and receptor density of 17 +/- 17 fmol/mg protein for cells in culture. The 50% inhibitory concentration (IC50) for atenolol was 470 microM and for ICI 118551 was 0.012 microM. Analysis of the ICI 118551 displacement curve indicates that greater than 90% of the receptors are of the beta 2-adrenergic class. Prostaglandins E1 or E2, vasoactive intestinal peptide, carbachol, phenylephrine, or platelet-activating factor did not affect either the maximal cAMP response or the isoproterenol dose-response relationship. Neither clonidine nor epinephrine plus propranolol altered cellular cAMP content, and cyclooxygenase inhibition did not change ...