beta2-adrenergic receptor gene polymorphisms in myasthenia gravis (MG)

The beta2-adrenergic receptor (beta2-AR) belongs to the group of G-protein coupled receptors and is present mainly on skeletal and cardiac muscle cells and lymphocytes. The gene encoding beta2-AR (ADRB2) displays a moderate degree of heterogeneity in the human population. The distribution of polymorphisms at amino acid positions 16, 27 and 164 is changed in asthma, hypertension and obesity. We have earlier reported a decreased density of the beta2-AR on peripheral blood mononuclear cells and the presence of beta2-AR antibodies in patients with MG. Since certain polymorphisms affect the function of the beta2-AR, it was of interest to analyse these in MG. Using allele-specific polymerase chain reaction amplification, we revealed an over-representation of homozygosity for Arg16 and a lower prevalence of homozygosity for Gly16 in MG patients compared with healthy individuals. The increased frequency of homozygosity for Arg16 was due to a contribution from patients with generalized MG but not from patients with only ocular disease. Homozygosity for Glu27 was negatively associated with both the presence of beta2-AR antibodies and severity of disease. Moreover, acetylcholine receptor (AChR) antibodies were more often present in patients being homozygous for Gln27. Our results imply that homozygosity for Arg16 confers susceptibility to generalized MG, and that certain polymorphisms at amino acid position 27 are associated with subgroups of patients.     

Interaction of the pesticide chlordimeform with adrenergic receptors in mouse brain: an in vitro study

Chlordimeform (N'(4-chloro-o-tolyl)-N, N-dimethylformamidine; CDM) is a formamidine insecticide/acaricide whose major active metabolite is its N-monomethyl analog, desmethylchlordimeform, (DCDM). While their pesticidal action in invertebrates appears to be related to activation of octopamine receptors, their mechanism of action in mammals has not been established. Because of similarities between octopamine and adrenergic receptors and suggestions of CDM and DCDM action on adrenoceptors, the in vitro interactions of CDM and DCDM with adrenoceptors were studied. In mouse brain membrane preparations CDM inhibited the binding of [³H]-clonidine to alpha₂- adrenoceptors and of [³H]-WB4101 to alpha₁-adrenoceptors with IC₅₀ values of 18.2 and 87 M, respectively. DCDM was a much more potent inhibitor, with IC₅₀ values toward alpha_2–, and alpha₁-adrenoceptors of 44 nM and 1 M, respectively. Both compounds were only weak inhibitors of the binding of [³H]-dihydroalprenolol to beta-adrenoceptors and of [³H]-quinuclidinyl benzilate to muscarinic receptors and were inactive toward benzodiazepines and gamma aminobutyric acid (GABA_A) receptors. Inhibition of [³H]-clonidine binding by both compounds was competitive, as indicated by a decreased receptor affinity without changes in receptor density. Interaction of CDM and DCDM with [³H]-WB4101 binding, on the other hand, was more complex, and not of the competitive type. These results show that CDM and its metabolite DCDM can interact directly in vitro with alpha-adrenergic receptors, suggesting that these receptors could mediate some of the effects of CDM and DCDM in vivo.     

The effect of propranolol on exercise induced tachycardia is determined by plasma concentration and the density of adrenergic receptors on leukocytes

Summary The chronotropic response to a single oral dose of propranolol in 23 healthy subjects has been related to the plasma propranolol concentration and the density of -adrenoceptors on peripheral polymorphonuclear leucocytes. The percentage reduction in exercise-induced tachycardia was significantly correlated with the log plasma propranolol concentration within subjects but not between subjects. Taking the concentration of the active metabolite 4-hydroxypropranolol into account did not improve the interindividual correlation. The reduction in exercise-induced tachycardia was significantly correlated with the maximum binding density of (¹²⁵I)-hydroxybenzylpindolol on polymorphonuclear leucocyte membrane fragments measured before medication. A response index (% reduction in exercise-induced tachycardia/plasma propranolol concentration) was correlated with the maximum binding density of (¹²⁵I)-hydroxybenzylpindolol (predrug) at 2 h (r_s=0.72), 4 h (r_s=0.84) and 6 h (r_s=0.73) after dosing. The data suggest that interindividual variation in the response to propranolol after a single oral dose is determined by interindividual differences both in plasma propranolol and adrenoceptor density.     

Relationship between the Mutation of IRS-1 Gene and β_3-adrenergic Receptor Gene

Ｏｂｅｓｉｔｙｉｓａｓｓｏｃｉａｔｅｄｗｉｔｈｉｎｓｕｌｉｎｒｅｓｉｓ ｔａｎｃｅ (ＩＲ) ,ｗｈｉｃｈｐｌａｙｓａｃｒｉｔｉｃａｌｒｏｌｅｉｎｔｈｅｄｅｖｅｌｏｐｍｅｎｔｏｆｔｙｐｅ 2ｄｉａｂｅｔｅｓｍｅｌｌｉｔｕｓ.ＴｈｅｍｅｃｈａｎｉｓｍｏｆＩＲｉｓｒｅｌａｔｅｄｔｏｔｈｅａｂｎｏｒｍａｌｉｔｉｅｓｏｆｉｎｓｕｌｉｎｒｅｃｅｐｔｏｒ,ｐｒｅ ｒｅｃｅｐｔｏｒ,ｐｏｓｔ ｒｅｃｅｐ ｔｏｒ ,ｒｅｓｕｌｔｉｎｇｉｎｄｅｆｅｃｔｉｖｅｍｅｔａｂｏｌｉｃｐａｔｈｗａｙｏｆｇｌｕｃｏｓｅ,ｌｉｐｉｄａｎｄ ｐｒ…     

抗心脏β_1和M_2受体自身抗体与老年扩张型心肌病(英文)

目的　观测抗心脏 β1和M2 受体的自身抗体和老年扩张型心肌病 (EDCM)的相关性。方法　分别以 β1和M2 受体细胞外第二环 197- 2 2 2和 16 9- 173氨基酸序列的合成肽作为抗原 ,来检测老年扩张型心肌病患者的血清 (EDCM组 ,n =32 ) ,以健康人血清为正常对照 (NC组 ,n =2 0 )。结果　EDCM组抗 β1受体自身抗体的阳性率为 37.5 % (12 / 32 ) ,NC组为 5 .0 %(1/ 2 0 ) (P <0 .0 5 ) ;EDCM组抗M2 受体自身抗体的阳性率为 40 .6 % (13/ 32 ) ,NC组为 10 .0 % (2 / 2 0 ) (P <0 .0 5 ) ;心功能II-III级患者两种受体的阳性率是心功能IV级的 2倍或以上。结论　抗心脏 β1与M2 受体自身抗体的产生与老年EDCM有关 ,推测这两种自身抗体可能参与老年EDCM患者心肌重构和 /或心力衰竭的病理生理过程。     

胺碘酮合用小剂量β受体阻滞剂治疗老年阵发房颤临床观察

目的 比较胺碘酮与小剂量β受体阻滞剂合用对老年阵发性房颤的疗效。方法 回顾分析30名老年阵发房颤患者,根据房颤复律后维持用药的不同,分为3组：单用胺碘酮组（n=11);单用β阻滞剂组（n=9);胺碘酮与小剂量β阻滞剂合用组（n=10)。比较3组患者用药后12个月中房颤控制情况及心室率、心脏传导情况。结果 单用胺碘酮组显效率54．5％,有效率45．5％,无效率0％;单用β受体阻滞剂组显效率22．2％,有效率44．5％,无效率33．3％;胺碘酮与小剂量β受体阻滞剂合用治疗房颤,显效率90％,有效率10％,其疗效明显优于单用胺碘酮（P＜0．05）或单用β阻滞剂（P＜0．01）组,且未见明显副作用：3组间心室率未见显著差别。结论 胺碘酮与小剂β受体阻滞剂合用可有效地控制老年阵发性心房纤颤的发作。     

Role of specific adrenergic and cholinergic receptors of the blood vessel wall in the regulation of blood clotting during stimulation of the vagus nerve

Experiments on dogs showed that if the specific adrenergic receptors of the blood vessel wall (- and -receptors) were blocked by phentolamine or inderal it still continued to produce tissue blood clotting factors after stimulation of the vagus nerve. No response of this type was observed to stimulation of the nerve after the cholinergic receptors had been blocked by atropine. It is concluded that hyperfibrinolysis and hypercoagulation developing after vagus nerve stimulation are due to excitation of cholinergic structures.Department of Normal Physiology, Chita Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. N. Filatov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 78, No. 8, pp. 19–22, August, 1974.     

Bolus doses of esmolol for the prevention of perioperative hyper-tension and tachycardia

The effectiveness of esmolol, an ultra short-acting cardioselective beta blocker, in the prevention and treatment of post-intubation haemodynamic perturbations, was investigated. Forty-eight ASA physical status I and II patients undergoing hysterectomy were randomly assigned to receive a single intravenous bolus of placebo, esmolol 100 mg, or esmolol 200 mg in a double-blind fashion. This was administered over 15 sec, and immediately followed by thiopentone 3-5 mg.kg-1, succinylcholine 1.5 mg.kg-1, and tracheal intubation 90 sec later. The heart rate following induction of anaesthesia was lower in the esmolol 200 mg group (P less than 0.01); following intubation, the increase in heart rate in the placebo group was greater than in the esmolol groups (P less than 0.05). The systolic blood pressure post-induction was lower in the esmolol 200 mg group (P less than 0.05); following intubation, however, no significant differences were seen among groups in systolic, diastolic, or mean blood pressures. Following tracheal intubation, the incidence of ventricular arrhythmias was lower in the esmolol groups (P less than 0.05). In summary, esmolol in 100 mg and 200 mg doses was effective in mitigating the haemodynamic response following tracheal intubation.     

β3-肾上腺能受体基因Trp64Arg变异与Ⅱ型糖尿病的关系

探讨中国人Ⅱ型糖尿病与β3-肾上腺能受体(β3-AR)基因Trp64Arg变异的关系。 方法采用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)技术对无亲缘关系的山东省汉族212例(Ⅱ型糖尿病组132例,非糖尿病组80例)的β3-肾上腺能受体基因Trp64Arg突变进行检测。 结果两组β3-ARTrp和Arg等位基因分布频率分别为0.84,0.16和0.87,O.13,二者无显著差异(P>0.05),提示β3-AR基因多态性与Ⅱ型糖尿病的发生无密切关联。但Arg纯合子体重指数、舒张压、血清甘油三脂、空腹血C肽水平较高(P     

Potentiation by vasopressin of adrenergic vasoconstriction in the rat isolated mesenteric artery

1. The aim of the present study was to investigate in rat mesenteric artery rings whether low concentrations of vasopressin could modify the contractile responses to noradrenaline and electrical stimulation of perivascular nerves.
2. Vasopressin (10⁻¹⁰–10⁻⁷ M) caused concentration-dependent contractions (pD₂=8.36±0.09). The V₁-receptor antagonist d(CH₂)₅Tyr(Me)AVP (10⁻⁹–10⁻⁸ M) produced parallel rightward shifts of the control curve for vasopressin. Schild analysis yielded a pA₂ value of 9.83 with a slope of 1.10±0.14.
3. Vasopressin (3×10 ⁻¹⁰ and 10⁻⁹ M) caused concentration-dependent potentiation of the contractions elicited by electrical stimulation (2–8 Hz; 0.2 ms duration for 30 s) and produced leftward shifts of the concentration-response curve for noradrenaline. The V₁-receptor antagonist induced concentration-dependent inhibitions of potentiation induced by vasopressin. The selective V₁-receptor agonist [Phe^*, Orn⁸]-vasotocin (3×10 ⁻¹⁰ and 10⁻⁹ M) induced potentiation of electrical stimulation-evoked responses which was also inhibited in the presence of the V₁ antagonist (10⁻⁸ M). In contrast, the V₂-receptor agonist deamino-8-D-arginine vasopressin (desmopressin 10⁻⁸–10⁻⁷ M) did not modify the electrical stimulation-induced responses and the V₂-receptor antagonist [d(CH₂)₅, D-Ile^*, Ile⁴, Arg⁸]-vasopressin (10⁻⁸–10⁻⁷ M) did not affect the potentiation evoked by vasopressin.
4. In artery rings contracted by 10⁻⁶ M noradrenaline in the presence of 10⁻⁶ M guanethidine and 10⁻⁶ M atropine, electrical stimulation (2, 4 and 8 Hz) produced frequency-dependent relaxations which were unaffected by 10⁻⁹ M vasopressin but abolished by 10⁻⁶ M tetrodotoxin.
5. Vasopressin also potentiated contractions elicited by KCl and contractions induced by addition of CaCl₂ to KCl depolarized vessels. The augmenting effects were inhibited by the V₁ antagonist.
6. In the presence of the calcium antagonist nifedipine (10⁻⁶ M), vasopressin failed to enhance the contractile responses to electrical stimulation, noradrenaline and KCl.
7. The results demonstrate that low concentrations of vasopressin strongly potentiate the contractions to adrenergic stimulation and KCl depolarization. This effect appears to be mediated by V₁ receptor stimulation which brings about an increase in calcium entry through dihydropyridine-sensitive calcium channels.