기관근의 수축성에 대한 말초성 Benzodiazepine수용체의 역할

Involvement of Peripheral Benzodiazepine Receptor on the Contractility of Canine Trachealis Muscle.

Non-neuronal high affinity binding sites for benzodiazepines have been found in many peripheral tissues inc1uding cardiac musc1e and vascu1ar‘ smooth musc1e， and have been designated as ’peripheral benzodiazepine receptor’ Benzodiazepines have been shown to induce relaxation of the ileal， vesical， and uterine smooth musc1es. However，it is sti11 unc1ear about possible involvement of pe디pheral benzodiazepine receptor on the contractility of trachealis musc1e. This study was performed to investigate the role of the peripheral benzodiazepine receptor on the contractility of canine trachealis musc1e. Canine trachealis musc1e strips of 15 mm long were suspended in an isolated organ bath containing 1 ml of physiological sa1t solution maintained at 370C， and aerated with 95% 02/5% CO2. Isometric myography was performed， and the resu1ts of the experiments were as follows: R05-4684， FGIN -1-27 and c10nazepam reduced a basal tone of isolated canine trachealis musc1e strip concentration dependent1y， re1axant actions of R05-4684 and FGIN -1-27 were antagonized by PK 11195， a peripheral benzodiazepine receptor antagonist. F1umazenil， a central type antagonist， did not antagonize the relaxant action of peripheral type agonists. Saturation binding assay of [3H]R05-4864 showed a high affinity(Kd=5.33:t 1.27nM，Bmax= 867.3:t 147.2 fmol/mg protein) binding site on the canine trachealis musc1e. R05-4684 suppressed the bethanechol-， 5-hydroxytryptamine- and histamine- induced contractions. Platelet activating factor (PAF) exerted strong and prolonged contraction in trachealis musc1e strip. Strong tonic contraction by P AF was attenuated by Ro 5-4684， but not by WEB 2086， a P AF antagonist. Based on these resu1ts， it is conc1uded that the peripheral benzodiazepine receptor mediates the inhibitory regulation of contracti1ty of canine trachealis musc1e.