Muscarinic Cholinergic Receptors in Peripheral Lung Tissue of Normal Subjects and of Patients with Chronic Obstructive Lung Disease

Abstract

Muscarinic cholinergic receptors have been identified and characterized by radioligand binding studies in human peripheral lung tissue. The tissue was obtained at thoracotomy of 12 patients, of whom four had chronic obstructive lung disease. The radioligand 1-quinuclidinyl [phenyl-4-3H]benzilate (3H-QNB) was used to label the muscarinic cholinergic receptors. Binding was saturable, protein dependent and showed a high affinity and stereospecificity. Specific binding could be inhibited by agonists and antagonists; molar inhibition constants determined for the agents used were of the same order of magnitude as those reported for 3H-QNB inhibition in various tissues of laboratory animals. Inhibition experiments with agonists resulted in Hill slopes which were significantly different from unity, indicating multiple binding sites. The stable GTP analogue guanyl-5'-imidodiphosphate had no effect on the Hill slopes of agonists or antagonists. The number of binding sites was significantly less in lung tissue from patients with chronic obstructive lung disease.

Stereoselective Synthesis and Biodistribution of Potent [11C]-Labeled Antagonists for Positron Emission Tomography Imaging of Muscarinic Receptors in the Airways

“…The organic layers were dried (MgSO4) and evaporated. The crude product (cis:trans ) 12:1) was crystallized from hexane at -18 °C, yielding 6 (7.35 (2R,5R)-2-tert-Butyl-5-cyclohexyl-5-phenyl-1,3-dioxolan-4-one (7). To a solution of 6 (15.8 g, 52.7 mmol) in THF (175 mL) was added Pd/C (10%, 10 mol %).…”

“…These observations indicate an altered drug/receptor interaction after prolonged treatment and with increasing age. This could be due to a change of pulmonary receptor density , or to an altered coupling of the receptors to the contraction mechanism of the smooth muscle cells.…”

Autonomic Nervous System Regulation of Airway Tone

“…No significant abnormalities have been found in muscarinic receptors in COPD. 15,16 Likewise, it is unknown if transmission in autonomic ganglia is altered in COPD. M2 muscarinic receptors are functional in patients with stable COPD 17 ; it is unknown if function is altered during acute exacerbations.…”