内源性和外源性速激肽对雪貂下食管括约肌非肾上腺素能非胆碱能抑制途径的激活作用。
Activation of non-adrenergic non-cholinergic inhibitory pathways by endogenous and exogenous tachykinins in the ferret lower oesophageal sphincter.
作者信息
Smid S D, Lynn P A, Templeman R, Blackshaw L A
机构信息
Royal Adelaide Hospital, Australia.
出版信息
Neurogastroenterol Motil. 1998 Apr;10(2):149-56. doi: 10.1046/j.1365-2982.1998.00092.x.
Repeated oesophageal acidification causes lower oesophageal sphincter (LOS) relaxation in the anaesthetized ferret which is mediated by a peripheral neurokinin (NK-1) receptor mechanism. Our aim in this study was to characterize neural pathways in the LOS activated by capsaicin and tachykinin receptor agonists in vitro. Circular muscle strips of LOS (two per animal) from a total of 24 ferrets were maintained in organ baths. Electrical field stimulation (EFS, 50 V, 5-50 Hz) caused frequency-dependent LOS relaxation which was abolished by tetrodotoxin (TTX; 10(-6) M: P < 0.001) and reduced by N(G)-nitro-L-arginine (L-NNA; 10(-4) M: P < 0.01). Substance P and [Sar9, Met (O2)11]-substance P (selective NK-1 agonist) caused dose-dependent relaxation, while the NK-2 receptor agonist [beta-Ala8]-NKA 4-10 evoked excitation. Capsaicin (10(-6) M) caused relaxation and desensitization that was overcome by long recovery periods and substance P dosing (10(-8) M). After pretreatment with the NK-1 receptor antagonist CP 99994 (10(-7) M), substance P (10(-8) M; P < 0.001) and capsaicin (10(-6) M: P < 0.01)-induced relaxations were reduced. In the presence of TTX (10(-6) M), excitation resulted in response to substance P (10(-8) M; P < 0.05) and [Sar9, Met (O2)11]-substance P (10(-8) M; P < 0.001), while the response to [beta-Ala8]-NKA 4-10 (10(-7) M) was unaffected. In the presence of L-NNA (10(-4) M), substance P and [Sar9, Met (O2)11]-substance P-induced relaxations were reduced (10(-8) M; P < 0.01), while the response to [beta-Ala8]-NKA 4-10 (10(-7) M) was unaffected. These results show that functional coupling between capsaicin-sensitive sensory neurones and NANC inhibitory neural pathways occurs via NK-1 receptors in the ferret LOS. NK-2 (and some NK-1) receptors activate non-neural excitatory mechanisms. Substance P and NK-1 receptors coupling sensory and NANC inhibitory neurones may be important in the reflex control of LOS motility.
反复食管酸化可导致麻醉雪貂的食管下括约肌（LOS）松弛，这是由外周神经激肽（NK-1）受体机制介导的。本研究的目的是在体外鉴定辣椒素和速激肽受体激动剂激活的LOS中的神经通路。从总共24只雪貂身上获取的LOS环形肌条（每只动物两条）置于器官浴槽中。电场刺激（EFS，50V，5 - 50Hz）引起频率依赖性的LOS松弛，该松弛被河豚毒素（TTX；10⁻⁶M：P < 0.001）消除，并被N⁰-硝基-L-精氨酸（L-NNA；10⁻⁴M：P < 0.01）减弱。P物质和[Sar⁹, Met（O²）¹¹]-P物质（选择性NK-1激动剂）引起剂量依赖性松弛，而NK-2受体激动剂[β-Ala⁸]-NKA 4-10引起兴奋。辣椒素（10⁻⁶M）引起松弛和脱敏，长时间恢复和给予P物质（10⁻⁸M）可克服这种情况。用NK-1受体拮抗剂CP 99994（10⁻⁷M）预处理后，P物质（10⁻⁸M；P < 0.001）和辣椒素（10⁻⁶M：P < 0.01）诱导的松弛减弱。在存在TTX（10⁻⁶M）的情况下，对P物质（10⁻⁸M；P < 0.05）和[Sar⁹, Met（O²）¹¹]-P物质（10⁻⁸M；P < 0.001）的反应导致兴奋，而对[β-Ala⁸]-NKA 4-10（10⁻⁷M）的反应未受影响。在存在L-NNA（10⁻⁴M）的情况下，P物质和[Sar⁹, Met（O²）¹¹]-P物质诱导的松弛减弱（10⁻⁸M；P < 0.01），而对[β-Ala⁸]-NKA 4-10（10⁻⁷M）的反应未受影响。这些结果表明，在雪貂LOS中，辣椒素敏感的感觉神经元与非肾上腺素能非胆碱能（NANC）抑制性神经通路之间通过NK-1受体发生功能偶联。NK-2（以及一些NK-1）受体激活非神经兴奋性机制。P物质和NK-1受体将感觉神经元与NANC抑制性神经元偶联，这可能在LOS运动的反射控制中起重要作用。
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