Kelsen S G, Zhou S, Anakwe O, Mardini I, Higgins N, Benovic J L
Department of Medicine, Temple University School of Medicine, Philadelphia 19140.
Am J Physiol. 1994 Oct;267(4 Pt 1):L456-63. doi: 10.1152/ajplung.1994.267.4.L456.
Catecholamines acting through the beta-adrenergic receptor (beta AR) coupled-adenylylcyclase system stimulate a variety of responses by airway epithelial cells which affect airway caliber and the response to inflammatory stimuli. Although the tracheobronchial epithelium (TBE) is composed of several phenotypically differentiated cell types, surprisingly little is known about the expression of the beta AR system by the major subpopulations of TBE cells (i.e., basal and columnar). We, therefore, examined the function of the beta AR system in columnar and basal cell-enriched populations of rabbit tracheocytes. Cells were collected from 35 rabbits in 17 separate experiments and separated into basal and columnar cell-enriched fractions by centrifugal elutriation. The columnar fraction demonstrated a significantly greater (P < 0.005) adenosine 3',5'-cyclic monophosphate (cAMP) response to isoproterenol (10(-9)-10(-5) M) than the basal cell-enriched fraction (i.e., 74.7 +/- 5.1 and 49.4 +/- 2.8 pmol/10(6) cells, in columnar and basal cell-enriched fractions, respectively, P < 0.0001) as well as a higher beta AR density (i.e., 8,678 +/- 840 and 4,754 +/- 406 beta AR sites/cell, respectively, P < 0.0001). However, when corrected for differences in cell size assessed from measurements of total cell protein, cAMP production per milligram protein and beta AR density per milligram protein were similar in the two cell fractions (P > 0.50 for both comparisons). beta AR subtype assessed by beta 1AR and beta 2AR subtype selective antagonists demonstrated that the beta 2AR subtype predominated (i.e., > 90%) in both cell populations (P > 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)
儿茶酚胺通过β-肾上腺素能受体(βAR)偶联的腺苷酸环化酶系统发挥作用,刺激气道上皮细胞产生多种反应,这些反应会影响气道口径以及对炎症刺激的反应。尽管气管支气管上皮(TBE)由几种表型分化的细胞类型组成,但令人惊讶的是,对于TBE细胞主要亚群(即基底细胞和柱状细胞)中βAR系统的表达了解甚少。因此,我们研究了兔气管细胞中富含柱状细胞和基底细胞群体的βAR系统功能。在17个独立实验中从35只兔子收集细胞,并通过离心淘析将其分离为富含基底细胞和柱状细胞的组分。柱状细胞组分对异丙肾上腺素(10^(-9)-10^(-5)M)的腺苷3',5'-环磷酸(cAMP)反应明显大于富含基底细胞的组分(即,柱状细胞和富含基底细胞的组分中分别为74.7±5.1和49.4±2.8 pmol/10^6细胞,P<0.0001),并且βAR密度更高(即,分别为8678±840和4754±406个βAR位点/细胞,P<0.0001)。然而,根据通过测量总细胞蛋白评估的细胞大小差异进行校正后,两个细胞组分中每毫克蛋白的cAMP产生量和每毫克蛋白的βAR密度相似(两种比较的P均>0.50)。通过β1AR和β2AR亚型选择性拮抗剂评估的βAR亚型表明,β2AR亚型在两个细胞群体中均占主导(即>90%)(P>0.5)。(摘要截断于250字)