血管活性肠肽。豚鼠结肠带中的舒张性神经递质。

Vasoactive intestinal peptide. Relaxant neurotransmitter in tenia coli of the guinea pig.

作者信息

Grider J R, Cable M B, Bitar K N, Said S I, Makhlouf G M

出版信息

Gastroenterology. 1985 Jul;89(1):36-42.

Abstract

Two main candidates have been proposed for the role of relaxant neurotransmitter in the intestine: (a) the purine nucleotide, 5'-adenosine triphosphate (ATP) and (b) the neuropeptide, vasoactive intestinal peptide (VIP). The candidacy of VIP is favored by its precise location in nerve fibers that innervate circular smooth muscle and tenia coli. We have used a photoaffinity analog of ATP, 3'-O-(4-Benzoyl)benzoyl ATP, that binds irreversibly to ATP receptors and inactivates them in the presence of light, and a specific VIP antiserum to examine the claims of VIP and ATP as relaxant neurotransmitters in tenia coli of the guinea pig. Both VIP and ATP caused dose-dependent, tetrodotoxin-insensitive relaxation of tenia coli. The effect of ATP was equipotent to that of its stable isostere alpha, beta-methylene ATP and resistant to degradation by adenosine deaminase, indicating interaction of ATP with purinergic-P2 receptors. Photoactivated 3'-O-(4-Benzoyl) benzoyl adenosine triphosphate selectively inhibited relaxation induced by ATP but had no effect on relaxation induced by VIP or by field (i.e., neural) stimulation. Vasoactive intestinal peptide antiserum (final dilution 1:60), on the other hand, inhibited relaxation caused by VIP and by field stimulation but had no effect on relaxation caused by ATP. Neither normal rabbit serum nor preneutralized VIP antiserum had any effect on relaxation induced by ATP, VIP, or field stimulation. Inhibition of neurally induced relaxation by VIP antiserum ranged from 52% +/- 7% (p less than 0.01) at the lowest frequency of stimulation to 15% +/- 4% (p less than 0.01) at the highest frequency, consistent with competitive interaction between antiserum and neurally released VIP. Near-maximal field stimulation at 1 Hz caused an eightfold (800% +/- 49%, p less than 0.01) increase in VIP release into the bathing medium. The results favor VIP (and probably peptide histidine isoleucine, a relaxant homologue known to be cosynthesized with VIP) as the main neural mediator of relaxation in tenia coli.

摘要

关于肠道中起舒张神经递质作用的物质，主要有两种候选物：（a）嘌呤核苷酸，5'-三磷酸腺苷（ATP）；（b）神经肽，血管活性肠肽（VIP）。VIP作为候选物更具优势，因为它精确地存在于支配环行平滑肌和结肠带的神经纤维中。我们使用了一种ATP的光亲和类似物，3'-O-(4-苯甲酰基)苯甲酰基ATP，它能不可逆地与ATP受体结合，并在光照下使其失活，还使用了一种特异性VIP抗血清，来检验VIP和ATP作为豚鼠结肠带舒张神经递质的说法。VIP和ATP都引起了结肠带剂量依赖性、对河豚毒素不敏感的舒张。ATP的作用与其稳定的等排体α,β-亚甲基ATP相当，且对腺苷脱氨酶的降解具有抗性，这表明ATP与嘌呤能P2受体相互作用。光活化的3'-O-(4-苯甲酰基)苯甲酰基三磷酸腺苷选择性地抑制了由ATP诱导的舒张，但对由VIP或场（即神经）刺激诱导的舒张没有影响。另一方面，血管活性肠肽抗血清（终浓度稀释1:60）抑制了由VIP和场刺激引起的舒张，但对由ATP引起的舒张没有影响。正常兔血清和预先中和的VIP抗血清对由ATP、VIP或场刺激诱导的舒张均无任何影响。VIP抗血清对神经诱导舒张的抑制作用在最低刺激频率时为52%±7%（p<0.01），在最高刺激频率时为15%±4%（p<0.01），这与抗血清和神经释放的VIP之间的竞争性相互作用一致。1Hz的近最大场刺激使VIP释放到浴液中的量增加了八倍（800%±49%，p<0.01）。结果表明，VIP（可能还有肽组氨酸异亮氨酸，一种已知与VIP共同合成的舒张同系物）是结肠带舒张的主要神经介质。