Weglarz Ludmiła, Grzanka Alicja, Kierot Jolanta, Wilczok Tadeusz
Katedry Biologii Molekularnej, Biochemii i Biofarmacji w Sosnowcu.
Wiad Lek. 2003;56(5-6):283-8.
The human beta 2-adrenoceptor is a member of the seven-transmembrane family of receptors. It is expressed in many cell types such as airway smooth muscle cells, neutrophils, eosinophiles, alveolar macrophages and airway epithelial cells. The beta 2-adrenoceptor agonists are the most important group of bronchodilator drugs used in the treatment of asthma. They are classified by their selectivity, affinity for the receptor, potency and pharmacological efficacy. The gene encoding the beta 2-adrenergic receptor is highly polymorphic in the human population. Polymorphism affecting amino acids 16, 27 and 164 are the most common and they have been shown to correlate with some clinical features of asthma, including airways reactivity. They can modulate the behaviour of the beta 2-receptor, altering ligand binding and the characteristics of down-regulation following agonist exposure. The homozygous glycine-16 (Arg-->Gly) variant of the beta 2-adrenoceptor is known to predispose to agonist-induced down-regulation and desensitization, and may play a role in the pathogenesis of asthma severity. The polymorphism at position 27 (Gln-->Glu) is associated with decreased airway responsiveness. The polymorphic variant 164 (Thr-->Ile) shows impaired agonist binding and decreased adenylyl cyclase activity. No convincing evidence has been presented demonstrating a linking of asthma per se with this receptor polymorphism.
人β2肾上腺素能受体是七跨膜受体家族的成员。它在许多细胞类型中表达，如气道平滑肌细胞、中性粒细胞、嗜酸性粒细胞、肺泡巨噬细胞和气道上皮细胞。β2肾上腺素能受体激动剂是治疗哮喘最重要的一类支气管扩张药物。它们根据选择性、对受体的亲和力、效力和药理作用进行分类。编码β2肾上腺素能受体的基因在人群中具有高度多态性。影响第16、27和164位氨基酸的多态性最为常见，并且已证明它们与哮喘的一些临床特征相关，包括气道反应性。它们可以调节β2受体的行为，改变配体结合以及激动剂暴露后下调的特征。已知β2肾上腺素能受体的纯合甘氨酸-16（精氨酸→甘氨酸）变体易导致激动剂诱导的下调和脱敏，并且可能在哮喘严重程度的发病机制中起作用。第27位（谷氨酰胺→谷氨酸）的多态性与气道反应性降低有关。多态性变体164（苏氨酸→异亮氨酸）表现出激动剂结合受损和腺苷酸环化酶活性降低。尚未有令人信服的证据表明哮喘本身与这种受体多态性有关联。
