Fernández E, Guo X, Vergara P, Jiménez M
Dept. of Physiology and Cell Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Life Sci. 1998;62(15):1303-15. doi: 10.1016/s0024-3205(98)00064-2.
The aim of this study was to investigate the nature of the non-adrenergic non-cholinergic (NANC) inhibitory transmitter of the circular muscle of the porcine ileum. For this purpose, the effects of putative NANC mediators i.e. NO, vasoactive intestinal polypeptide (VIP) and ATP were measured in isolated organ bath experiments (in basal conditions and after incubation with neostigmine 3 x 10[-5] M) and using the microelectrode technique. The NO donor sodium nitroprusside (NaNP) up to 10(-4) M, VIP up to 10(-7) M and ATP up to 10(-4) M failed to cause significant relaxation in the basal state. However, all of them induced marked relaxations when the tissue had been preincubated with neostigmine (3 x 10[-5] M) which was added to increase basal mechanical activity. The resting membrane potential (RMP) was unaffected by NaNP(up to 10(-4) M and VIP up to 10(-7) M whereas ATP (up to 10[-4] M) induced a transient hyperpolarization. The inhibitory junction potentials (IJPs) induced by electrical field stimulation (EFS) were not affected by N omega-nitro-L-arginine (L-NNA) (10[-4] M) whereas suramin, a purinoceptor antagonist, decreased (10[-4] M) or abolished (10[-3] M) the IJPs. Relaxations induced by ATP in neostigmine preincubated tissue were resistant to 10(-6) M tetrodotoxin, an axonal blocker, and inhibited by suramin. Apamin (10[-6] M, a small conductance calcium activated potassium channel blocker, completely abolished the IJP (n=5) and significantly decreased the relaxation induced by ATP (n=5). The present data provide support to the hypothesis that ATP is the NANC inhibitory transmitter in the porcine ileum acting on P2 muscular receptors. Nevertheless, VIP and NaNP do also cause relaxation of preparations preincubated with neostigmine.
本研究的目的是探究猪回肠环形肌非肾上腺素能非胆碱能（NANC）抑制性递质的性质。为此，在离体器官浴实验中（在基础条件下以及与新斯的明3×10⁻⁵ M孵育后）并使用微电极技术，测定了假定的NANC介质即一氧化氮（NO）、血管活性肠肽（VIP）和三磷酸腺苷（ATP）的作用。高达10⁻⁴ M的NO供体硝普钠（NaNP）、高达10⁻⁷ M的VIP和高达10⁻⁴ M的ATP在基础状态下未能引起显著舒张。然而，当组织用新斯的明（3×10⁻⁵ M）预孵育以增加基础机械活性后，它们都诱导了明显的舒张。静息膜电位（RMP）不受高达10⁻⁴ M的NaNP和高达10⁻⁷ M的VIP影响，而高达10⁻⁴ M的ATP诱导了短暂的超极化。电场刺激（EFS）诱导的抑制性接头电位（IJP）不受Nⁿ-硝基-L-精氨酸（L-NNA）（10⁻⁴ M）影响，而嘌呤受体拮抗剂苏拉明在10⁻⁴ M时降低或在10⁻³ M时消除IJP。ATP在新斯的明预孵育组织中诱导的舒张对轴突阻滞剂10⁻⁶ M河豚毒素有抗性，并被苏拉明抑制。蜂毒明肽（10⁻⁶ M，一种小电导钙激活钾通道阻滞剂）完全消除IJP（n = 5）并显著降低ATP诱导的舒张（n = 5）。目前的数据支持以下假设：ATP是猪回肠中作用于P2肌肉受体的NANC抑制性递质。然而，VIP和NaNP也确实会使用新斯的明预孵育的制剂舒张。
