Reinheimer T, Möhlig T, Zimmermann S, Höhle K D, Wessler I
Department of Pharmacology, University of Mainz and Academic St. Hildegardis Hospital, Mainz, Germany.
Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):534-8. doi: 10.1164/ajrccm.162.2.9911094.
Isolated human bronchi and rat tracheae were incubated in organ baths to measure histamine release. The calcium ionophore A23187, 3 micromol/L in rat trachea and 10 micromol/L in human bronchi, stimulated histamine release by 145 +/- 50% (n = 6) and 270 +/- 48% (n = 7) above the prestimulation level, respectively. Acetylcholine (100 pmol/L; human bronchi) or oxotremorine (1, 100, 10,000 nmol/L; rat trachea) did not affect the spontaneous histamine release. In rat tracheae neither acetylcholine nor oxotremorine inhibited A23187-evoked histamine release, whereas 100 pmol/L acetylcholine significantly suppressed the evoked histamine release in human bronchi by 86%. For receptor characterization the following subtype-specific muscarinic receptor antagonists were applied: pirenzepine (M1 subtype), para-fluorohexahydrosiladifendiol (pFHHSiD; similar affinities at human cloned M1-, M3-, and M4-receptors), AF-DX 116 (M2 subtype), and clozapine (antagonist at cloned M1-, M2-, M3-receptors; agonist at cloned M4-receptors). Pirenzepine, pFHHSiD, AF-DX 116, and clozapine (100 nmol/L each) antagonized the inhibitory effect of 100 pmol/L acetylcholine by 83 +/- 20% (n = 6), 83 +/- 9% (n = 8), 50 +/- 14% (n = 6), and 35 +/- 7% (6). In conclusion, a species difference exists in the cholinergic control of histamine release between human and rat airways. In human airways muscarinic receptors most likely of the M1 subtype are involved in the inhibitory control of mast cell function, whereas such an inhibitory pathway does not exist in the rat trachea.
将分离出的人支气管和大鼠气管置于器官浴槽中孵育，以测定组胺释放量。钙离子载体A23187，在大鼠气管中浓度为3 μmol/L，在人支气管中浓度为10 μmol/L，分别使组胺释放量比刺激前水平增加了145±50%（n = 6）和270±48%（n = 7）。乙酰胆碱（100 pmol/L；人支气管）或氧化震颤素（1、100、10000 nmol/L；大鼠气管）不影响组胺的自发释放。在大鼠气管中，乙酰胆碱和氧化震颤素均不抑制A23187诱发的组胺释放，而100 pmol/L乙酰胆碱可使诱发的人支气管组胺释放量显著降低86%。为进行受体特性分析，应用了以下亚型特异性毒蕈碱受体拮抗剂：哌仑西平（M1亚型）、对氟六氢硅二酚（pFHHSiD；对人克隆的M1、M3和M4受体亲和力相似）、AF-DX 116（M2亚型）和氯氮平（对克隆的M1、M2、M3受体为拮抗剂；对克隆的M4受体为激动剂）。哌仑西平、pFHHSiD、AF-DX 116和氯氮平（各100 nmol/L）分别使100 pmol/L乙酰胆碱的抑制作用拮抗了83±20%（n = 6）、83±9%（n = 8）、50±14%（n = 6）和35±7%（n = 6）。总之，人与大鼠气道在组胺释放的胆碱能控制方面存在种属差异。在人气道中，最有可能是M1亚型的毒蕈碱受体参与了对肥大细胞功能的抑制性控制，而在大鼠气管中不存在这样的抑制途径。
