Imoto A, Inoue R, Tanaka M, Ito Y
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Auton Nerv Syst. 1998 Jun 10;70(3):189-99. doi: 10.1016/s0165-1838(98)00051-4.
The pharmacological properties of non-adrenergic non-cholinergic (NANC) inhibitory neurotransmission were investigated in the rabbit choledocho-duodenal junction (CDJ), using the microelectrode and tension recording methods. L-NAME (10(-4) M) and apamin (5 X 10 (-6) M) suppressed NANC relaxation evoked by electrical field stimulation (EFS) in the presence of atropine and guanethidine (each 10(-6) M) to a similar extent (to about 40% of the initial control). However, combined application of L-NAME (10(-4) M) and apamin (5 X 10(-6) M) did not abolish it. EFS also evoked biphasic inhibitory junction potentials (IJPs) consisting of initial fast and slow sustained components in the presence of atropine and guanethidine (each 10(-6) M). Apamin (5 X 10(-8)-5 X 10(-6) M) dose-dependently suppressed the initial fast component by about 70%. In contrast, L-NAME (10(-4) M) did not affect either the amplitude of IJP or the resting membrane potential. PACAP-38 (> 10(-8) M) dose-dependently hyperpolarized the smooth muscle membrane of rabbit CDJ followed by a slow repolarization to the original level. After pretreatment with apamin (5 X 10(-7) M), PACAP-38 (10(-6) M) failed to evoke membrane hyperpolarization. During repolarization in the continued presence of PACAP-38, the amplitude of initial fast component of IJP was reduced to about 40-60% of control value, while that of the slow one was unaffected. A similar suppression of initial fast component of IJP (about 40% of the control value) also occurred after application of PACAP (6-38), a PACAP antagonist, or prolonged treatment with monoclonal antibodies to PACAP-27 or PACAP-38. Furthermore, the substantial part of residual fast IJP in the presence of PACAP (6-38) was suppressed by desensitization to alpha,beta-methylene ATP (10(-3) M). These results indicate that in rabbit CDJ NANC relaxation consists mainly of apamin- and L-NAME-sensitive components, which occur in a membrane potential dependent (through membrane hyperpolarization) and independent fashion, respectively. It has further been suggested that PACAP, together with a smaller contribution of ATP, may be involved as the principal apamin-sensitive transmitter in NANC relaxation of this muscle.
采用微电极和张力记录方法，研究了兔胆总管十二指肠连接处（CDJ）非肾上腺素能非胆碱能（NANC）抑制性神经传递的药理学特性。在存在阿托品和胍乙啶（各10⁻⁶ M）的情况下，L - 精氨酸甲酯（10⁻⁴ M）和蜂毒明肽（5×10⁻⁶ M）对电场刺激（EFS）诱发的NANC舒张的抑制程度相似（降至初始对照的约40%）。然而，联合应用L - 精氨酸甲酯（10⁻⁴ M）和蜂毒明肽（5×10⁻⁶ M）并未完全消除该舒张反应。在存在阿托品和胍乙啶（各10⁻⁶ M）的情况下，EFS还诱发了由初始快速和缓慢持续成分组成的双相抑制性接头电位（IJP）。蜂毒明肽（5×10⁻⁸ - 5×10⁻⁶ M）剂量依赖性地抑制初始快速成分约70%。相比之下，L - 精氨酸甲酯（10⁻⁴ M）对IJP的幅度或静息膜电位均无影响。垂体腺苷酸环化酶激活肽 - 38（PACAP - 38，>10⁻⁸ M）剂量依赖性地使兔CDJ的平滑肌膜超极化，随后缓慢复极化至原始水平。用蜂毒明肽（5×10⁻⁷ M）预处理后，PACAP - 38（10⁻⁶ M）未能诱发膜超极化。在持续存在PACAP - 38的复极化过程中，IJP初始快速成分的幅度降至对照值的约40% - 60%，而缓慢成分的幅度未受影响。应用PACAP拮抗剂PACAP（6 - 38）或用抗PACAP - 27或PACAP - 38单克隆抗体进行长期处理后，也出现了对IJP初始快速成分的类似抑制（约为对照值的40%）。此外，在存在PACAP（6 - 38）时，残余快速IJP的大部分被α,β - 亚甲基ATP（10⁻³ M）脱敏所抑制。这些结果表明，在兔CDJ中，NANC舒张主要由蜂毒明肽和L - 精氨酸甲酯敏感成分组成，它们分别以膜电位依赖性（通过膜超极化）和非依赖性方式发生。进一步表明，PACAP连同较小贡献的ATP，可能作为主要的蜂毒明肽敏感递质参与该肌肉的NANC舒张。
