Disease relevance of methacholine

• Euglycemic hyperinsulinemia augmented the LBF response to MCh by - 50% in C (P < 0.05 vs saline) but not in OB and NIDDM [1].
• In the present investigation, cholinergic stimulation was produced by administering the selective muscarinic agent methacholine (MCh) and ventricular vulnerability was assessed by measuring the repetitive extrasystole (RE) threshold [2].
• Mild airway obstruction and increased airway responsiveness to inhaled MCH but not to MBS suggest that structural changes in distal airways are involved and not autonomic nerve dysfunction [3].
• Five of the seven patients with FAP showed bronchial hyperreactivity to MCh, and PD20 to MCh was significantly lower than that of the normal subjects (p < 0.01) [4].
• In mice, respiratory syncytial virus (RSV) infection can enhance the consequences of allergic airway sensitization, resulting in lung eosinophilia and the development of airway hyperresponsiveness (AHR) to inhaled methacholine (MCh) [5].

High impact information on methacholine

• During the 2-h SRIF infusion, insulin levels fell, and FFA levels rose from 474+/-22 to 1,042+/-116 micromol (P < 0.01); Mch-induced vasodilation was reduced by approximately 20% (P < 0.02, saline vs. SRIF, ANOVA) [6].
• Mch-induced vasodilation relative to baseline was reduced by approximately 20% in response to the raised FFA levels in both groups (P < 0.05, saline vs. FFA, ANOVA) [6].
• MCh induced increments in LBF were approximately 40% and 55% lower in OB and NIDDM, respectively, as compared with C (P < 0.05) [1].
• Regression analysis revealed a significant inverse correlation between the maximal LBF change in response to MCh and body fat content [1].
• To investigate the cellular sources and the secretory control of these nasal proteins in vivo, 34 adult subjects underwent nasal provocation tests with methacholine (MC), histamine (H), and gustatory stimuli [7].

Chemical compound and disease context of methacholine

• RESULTS: Infusion of Mch increased FBF significantly less in patients with renal failure than in controls (198 vs 374%, P<0.001), whereas no significant difference was seen regarding the vasodilatation induced by SNP (278 vs 269%) [8].
• 3. The cholinergic agonists induced contracture of the ligament, but had quite different kinetics, the rate of rise of the contracture being fastest for ACh and decreasing in the following order: CCh, MeACh and nicotine [9].
• The relatively good effect of THEO on small airway obstruction caused by MeCh was not augmented by TER or IPRA [10].
• BALB/c mice were sensitized and challenged with ovalbumin (OVA) to develop the asthmatic features such as airway hyperresponsiveness: allergen induced airway constriction and airway hyperreactivity (AHR) to methacholine (MCh), and pulmonary inflammation [11].
• TER inhibited both MeCh- and LTD4-induced airway obstruction about equally, whereas IPRA was effective on the MeCh-induced obstruction only [10].

Biological context of methacholine

• Our study showed significant linkage between airway responsiveness to MTCH and D2S1780 on chromosome 2 (P<.00002) and provided suggestive evidence (P<.002) for six additional possible QTLs: D10S1435 and D22S685, for FEV1; D16S412, for FVC; D19S433, for airway responsiveness to MTCH; D1S518, for TIgE; and D4S1647, for skin reactivity to cockroach [12].
• Maximal isometric contraction to MCh increased from 1911 +/- 245 (Generation 2) to 6693 +/- 850 g/gM (Generation 5) (P less than 0.005) [13].
• Furthermore, we observed that after constriction had already been induced by MCh, following a DI, bronchodilation occurred in the healthy subjects but further bronchoconstriction occurred in the subjects with asthma [14].
• Airway function was monitored by changes in lung resistance (RL) and dynamic compliance (Cdyn) to methacholine (MCh) inhalation after anti-VLA-4 [15].
• In contrast, generation of isometric tension in trachealis, morphometric measurements of tracheal ASM, tracheal myosin content, and dose-response curves for MCh of explanted intraparenchymal bronchi failed to correspond to the in vivo phenotype of airway reactivity [16].

Anatomical context of methacholine

• Compared with MCh only piglets, the thickness of the outer airway wall (between the outer border of the smooth muscle and the surrounding lung parenchyma) was increased (p < 0.05) in engorged only and engorged plus MCh piglets [17].
• Airway responsiveness to inhaled MCh was assessed and numbers of lung eosinophils were monitored [5].
• The influence of pulmonary vascular congestion on the response of the airways and lung tissue to low doses of inhaled methacholine (MCh) was studied by inflating a balloon catheter in the left atrium of the heart in six piglets, with an additional five piglets serving as control animals [17].
• Perfusion with lipopolysaccharide (LPS) had no effect on pulmonary resistance or pulmonary artery pressure, but induced airway hyperreactivity (AHR) to methacholine (MCh) and pulmonary vascular hyperreactivity (VHR) to platelet-activating factor (PAF) [18].
• 5. Simultaneous measurement of cytosolic (fluo-3 AM) and mitochondrial (rhod-2 AM) Ca2+ responses revealed that Ca2+ elevations in the cytosol evoked by either MCh or kainate were translated into long-lasting Ca2+ elevations in subpopulations of mitochondria [19].

Associations of methacholine with other chemical compounds

• ACh and MCh both caused dose-dependent vasodilation, with EC50 values of 537 and 52 nmol/L, respectively [20].
• Concentration-response curves were generated in the same strips with methacholine (MCh) and potassium chloride (KCl) in vitro [13].
• I.a. infusion of Mch and SNP increased forearm blood flow from 1.9 to 14.9 and from 1.8 to 12.1 ml x min-1 x 100 ml-1, respectively (Mch vs SBP N.S.).(ABSTRACT TRUNCATED AT 250 WORDS)[21]
• CONCLUSION: The results show that the vascular endothelium is responsive to repeated stimulation both with MCH and with DDAVP [22].
• 3. During a Ca2+ wave evoked by MCh, mitochondrial membrane potential was often either depolarized (21 % of mitochondria) or hyperpolarized (20 % of mitochondria), as measured by changes in the fluorescence of 5,5',6,6'-tetrachloro-1,1',3, 3'-tetraethylbenzimidazole carbocyanine iodide (JC-1) [19].

Gene context of methacholine

• The M2-/- mice showed significantly enhanced in vivo bronchoconstrictor responses to vagal stimulation or MCh administration [23].
• The reduced hypotensive response of M3-/- mice to MCh suggests M3 mAChRs contribute to peripheral vasodilation [23].
• The EC50 values for MCh-induced ERK activation in both cell types were essentially identical and similar to that for JNK activation in CHO-m3 cells, suggesting little amplification of the response [24].
• In response to MCh infusion, both the net release of TPA antigen and increment in TPA activity increased markedly and to similar extents in both groups (P < .01 throughout) [25].
• In addition, GRK3 -/- mice displayed an altered HR recovery from MCh-induced bradycardia [26].

Analytical, diagnostic and therapeutic context of methacholine

• Low-dose inhaled MCh (0.3 mg/ml) increased Raw and Rti in the control group by 10.8 +/- 10.3% and 42.2 +/- 29.5%, respectively [17].
• Recipients were challenged with aerosolized OA or bovine serum albumin (BSA) (5% wt/vol) and analyzed for changes in lung resistance (RL), airway responsiveness to inhaled methacholine (MCh), and bronchoalveolar lavage (BAL) cells [27].
• Dynamic narrowing of intraparenchymal airways after maximal MCh stimulation was assessed by video microscopy [28].
• First we examined the FEV1 and Raw in seven patients with FAP and in six normal subjects, then we administered aerosols of increasing concentrations of MCh (0.075 to 25 mg/ml) at about 5-min intervals via a nebulizer controlled by a dosimeter [4].
• We studied leg blood flow (LBF) responses to graded intrafemoral artery infusion of the endothelium-dependent vasodilator methacholine chloride (MCh) and to a 4-h hyperinsulinemic euglycemic clamp (120 mU/m(2) x min) in 10 PCOS, before and after 3 months treatment with Tgz (600 mg/d) [29].

References