Acheson A, Rayment S, Eames T, Mundey M, Nisar P, Scholefield J, Wilson V G
Department of Surgery, The University of Nottingham Medical School, Queen's Medical Centre, Clifton Boulevard, Nottingham, United Kingdom.
Neurogastroenterol Motil. 2009 Mar;21(3):335-45. doi: 10.1111/j.1365-2982.2008.01250.x.
Nitric oxide is widely established as an important neurotransmitter in the control of anal sphincter tone; although, a number of other transmitters have also been tentatively implicated. Whilst alpha-adrenoceptor antagonists reduce anal sphincter pressure in man, the role of noradrenaline as a possible transmitter is poorly characterised. We have investigated the contribution of these transmitters to neurogenic relaxations, and evaluated the possible role of a non-nitrergic, non-adrenergic transmitter. The magnitude and duration of neurogenic responses were examined by measuring responses to electrical field stimulation (EFS) in segments of sheep internal anal sphincter following the development of spontaneous myogenic tone. Neurogenic relaxations induced by EFS were significantly reduced in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME) suggesting major involvement of nitric oxide as a neurotransmitter. The duration of neurogenic relaxations was inversely related to the frequency of EFS, with contractile responses often manifest at higher frequencies. The duration of relaxations at high frequencies of EFS was increased by bretylium (adrenergic neurone blocker) and prazosin (alpha(1)-adrenoceptor antagonist). At higher frequencies of EFS, 60% of preparations also produced a residual non-nitrergic, non-adrenergic, apamin-sensitive relaxation which was unaffected by vasoactive intestinal polypeptide (VIP) and inhibitors of purinergic responses [suramin, pyridoxal-phosphate-6-azophenyl 2',4' disulfonic acid (PPADS) and alpha,beta-methylene adenosine triphosphate (ATP)]. However, MRS2179 (P2Y(1) receptor antagonist) showed a modest inhibitory effect. We conclude that endogenous noradrenaline acts via postjunctional alpha(1)-adrenoceptors to antagonize neurogenic relaxations that are largely mediated by nitric oxide. Our results indicate the involvement of a non-nitrergic, non-adrenergic, apamin-sensitive transmitter which is inhibited by MRS2179, suggesting a possible role for purines.
一氧化氮作为控制肛门括约肌张力的一种重要神经递质已被广泛认可；不过，也有一些其他递质也被初步认为与之有关。虽然α-肾上腺素能受体拮抗剂可降低人体肛门括约肌压力，但去甲肾上腺素作为一种可能的递质，其作用尚不清楚。我们研究了这些递质对神经源性舒张的作用，并评估了一种非一氧化氮能、非肾上腺素能递质的可能作用。通过测量在羊肛门内括约肌节段自发产生肌源性张力后对电场刺激（EFS）的反应，来检测神经源性反应的幅度和持续时间。在存在N（G）-硝基-L-精氨酸甲酯（L-NAME）的情况下，EFS诱导的神经源性舒张明显减弱，这表明一氧化氮作为神经递质起主要作用。神经源性舒张的持续时间与EFS的频率呈负相关，在较高频率时通常会出现收缩反应。溴苄铵（肾上腺素能神经元阻断剂）和哌唑嗪（α（1）-肾上腺素能受体拮抗剂）可延长EFS高频时的舒张持续时间。在EFS较高频率时，60%的标本还产生了一种残余的非一氧化氮能、非肾上腺素能、对蜂毒明肽敏感的舒张，该舒张不受血管活性肠肽（VIP）和嘌呤能反应抑制剂[苏拉明、磷酸吡哆醛-6-偶氮苯2'，4'-二磺酸（PPADS）和α，β-亚甲基三磷酸腺苷（ATP）]的影响。然而，MRS2179（P2Y（1）受体拮抗剂）显示出适度的抑制作用。我们得出结论，内源性去甲肾上腺素通过节后α（1）-肾上腺素能受体发挥作用，拮抗主要由一氧化氮介导的神经源性舒张。我们的结果表明存在一种非一氧化氮能、非肾上腺素能、对蜂毒明肽敏感的递质，该递质受MRS2179抑制，提示嘌呤可能发挥作用。
