Manzini S, Maggi C A, Meli A
Eur J Pharmacol. 1985 Jul 31;113(3):399-408. doi: 10.1016/0014-2999(85)90088-3.
The nature of the inhbitory non-adrenergic non-cholinergic (NANC) neurotransmitter responsible for neurogenic relaxation of rat duodenum was studied with in vitro techniques. Adenosine 5'-triphosphate (ATP)(1 mM), gamma-aminobutyric acid (GABA, 1 mM), dimethylphenylpiperazinium (DMPP, 0.1 mM) and field stimulation (60 V, 2 ms, 0.1 Hz) produced transient relaxation followed by rebound contraction. In contrast vasoactive intestinal polypeptide (VIP) (0.3 microM) and noradrenaline (1 microM) induced relaxation which set in more slowly and lasted longer. Tetrodotoxin (0.85 microM) abolished field stimulation-induced relaxation but not ATP-, VIP- or noradrenaline-induced relaxation. Nucleotide pyrophosphatase (0.25 U/ml), but not the proteolytic enzyme alpha-chymotrypsin (2 U/ml), selectively antagonized NANC relaxation. The rank order of potency of various adenine derivatives for inducing relaxation was adenosine-5'-triphosphate greater than adenosine-5'-diphosphate much greater than adenosine greater than adenosine-5'-monophosphate. ATP-induced relaxation was selectively antagonized by the putative P2 purinoceptor antagonist reactive blue 2, but unaffected by the selective P1 purinoceptor antagonist 8-phenyltheophylline. The duration of ATP- as well as beta-gamma-methylene adenosine-5'-triphosphate (a stable analogue of ATP)-induced relaxation was similar and was unaffected by indomethacin 10 microM (which abolished the rebound contraction). In those preparations whose contractile tone was increased by using a high-K+ medium the ability of ATP to elicit relaxation was markedly reduced, while GABA- and DMPP-induced relaxation was abolished. On the other hand, ATP-, GABA- and DMPP-induced relaxation of the tonic component of 5-hydroxytryptamine (5-HT)(0.1 mM)-induced contraction was similar to that observed in control conditions. These findings add further weight to the proposal that endogenous ATP is involved in determining NANC relaxation of rat duodenum.
采用体外技术研究了负责大鼠十二指肠神经源性舒张的抑制性非肾上腺素能非胆碱能（NANC）神经递质的性质。三磷酸腺苷（ATP，1 mM）、γ-氨基丁酸（GABA，1 mM）、二甲基苯基哌嗪（DMPP，0.1 mM）和场刺激（60 V，2 ms，0.1 Hz）可产生短暂舒张，随后出现反跳性收缩。相比之下，血管活性肠肽（VIP，0.3 microM）和去甲肾上腺素（1 microM）诱导的舒张起效更慢，持续时间更长。河豚毒素（0.85 microM）可消除场刺激诱导的舒张，但不能消除ATP、VIP或去甲肾上腺素诱导的舒张。核苷酸焦磷酸酶（0.25 U/ml）而非蛋白水解酶α-糜蛋白酶（2 U/ml）可选择性拮抗NANC舒张。各种腺嘌呤衍生物诱导舒张的效力顺序为：三磷酸腺苷＞二磷酸腺苷＞腺苷＞一磷酸腺苷。ATP诱导的舒张可被假定的P2嘌呤受体拮抗剂反应性蓝2选择性拮抗，但不受选择性P1嘌呤受体拮抗剂8-苯基茶碱的影响。ATP以及β-γ-亚甲基三磷酸腺苷（ATP的稳定类似物）诱导舒张的持续时间相似，且不受10 microM吲哚美辛（可消除反跳性收缩）的影响。在使用高钾培养基使收缩张力增加的那些标本中，ATP引发舒张的能力明显降低，而GABA和DMPP诱导的舒张则被消除。另一方面，ATP、GABA和DMPP对5-羟色胺（5-HT，0.1 mM）诱导收缩的紧张性成分的舒张作用与在对照条件下观察到的相似。这些发现进一步支持了内源性ATP参与决定大鼠十二指肠NANC舒张的观点。
