Itoh H, Sakai J, Imoto A, Creed K E
Department of Pharmacology, School of Medicine, Kyushu University, Japan.
J Smooth Muscle Res. 1995 Jun;31(3):67-78. doi: 10.1540/jsmr.31.67.
Smooth muscle cells distributed in the visceral organs are under the control of the autonomic nervous system, and contraction or relaxation of the muscle cells plays an important physiological role in the control of blood pressure, motility of the digestive, respiratory and urinary tracts and secretion. Recent physiological, pharmacological and histochemical investigations indicate that neurotransmitters other than acetylcholine or noradrenaline are involved in peripheral autonomic neuro-effector transmission, and these neurotransmitters are generally termed non-adrenergic, non-cholinergic (NANC) neurotransmitters. The neurotransmitters responsible for excitatory and inhibitory NANC neurotransmission (e-NANC and i-NANC respectively) have not been conclusively identified, but ATP, nitric oxide (NO) and peptides such as VIP and substance P are candidates for these roles. In this review, we discuss the possible role of ATP and NO as e- or i-NANC neurotransmitter in the digestive, respiratory and urinary tracts. Much of the work on NANC innervation in the digestive tract has been carried out on the circular muscle layers of the ileum. This receives inhibitory NANC innervation with ATP responsible for fast relaxation and VIP, and possibly NO, for the slow response. Early and late excitatory junction potentials can be recorded in the presence of atropine. The second is due to substance P since it is blocked in the presence of spantide and by desensitization of the tissue with high doses of substance P. The transmitter responsible for the early NANC contraction has not been identified. Electrical field stimulation (EFS) applied to the tracheal smooth muscle during contraction induced by 5-HT in the presence of atropine and guanethidine elicited monophasic NANC relaxation. By contrast, NANC relaxation elicited in the smaller airways was biphasic, comprising an initial fast component followed by a second slow one. L-NAME selectively abolished the first component without affecting the second. VIP-antagonists or alpha-chymotrypsin considerably attenuated the amplitude of the L-NAME insensitive relaxation. These results indicate that at least two neurotransmitters, possibly NO or NO-containing compounds and VIP, are involved in i-NANC neurotransmission in the airway. In the urinary bladder a large, transient atropine resistant contraction occurs in response to pelvic nerve stimulation. This is blocked by alpha, beta methylene ATP suggesting that it is due to ATP. There is no evidence of inhibitory innervation. In the urethra contraction is completely blocked by atropine and guanethidine; a rapid NANC relaxation is abolished by drugs that block NO synthesis. Nerves containing peptides supply both urethra and bladder and may also be involved. These results suggest that all visceral smooth muscles may receive inhibitory NANC innervation involving NO. ATP produces contraction of the urinary bladder but relaxation of the digestive tract. The role of peptides is not yet clear but there is evidence that substance P may be an excitatory transmitter and VIP an inhibitory transmitter in many organs.
分布在内脏器官的平滑肌细胞受自主神经系统控制,这些肌细胞的收缩或舒张在血压调节、消化、呼吸和泌尿系统的蠕动及分泌控制中发挥着重要的生理作用。近期的生理学、药理学和组织化学研究表明,除乙酰胆碱或去甲肾上腺素外,其他神经递质也参与外周自主神经 - 效应器传递,这些神经递质通常被称为非肾上腺素能、非胆碱能(NANC)神经递质。负责兴奋性和抑制性NANC传递(分别为e - NANC和i - NANC)的神经递质尚未得到最终确定,但三磷酸腺苷(ATP)、一氧化氮(NO)以及诸如血管活性肠肽(VIP)和P物质等肽类是这些作用的候选者。在本综述中,我们讨论了ATP和NO作为e - NANC或i - NANC神经递质在消化、呼吸和泌尿系统中可能发挥的作用。关于消化道NANC神经支配的许多研究是在回肠的环行肌层进行的。该部位接受抑制性NANC神经支配,ATP负责快速舒张,VIP以及可能还有NO负责缓慢反应。在阿托品存在的情况下可记录到早期和晚期兴奋性接头电位。第二个电位是由于P物质引起的,因为在spantide存在以及用高剂量P物质使组织脱敏时该电位被阻断。负责早期NANC收缩的递质尚未确定。在阿托品和胍乙啶存在的情况下,当5 - 羟色胺(5 - HT)诱导气管平滑肌收缩时,施加电场刺激(EFS)可引起单相NANC舒张。相比之下,较小气道中引发的NANC舒张是双相的,包括一个初始的快速成分和随后的第二个缓慢成分。L - 精氨酸甲酯(L - NAME)选择性地消除了第一个成分而不影响第二个成分。VIP拮抗剂或α - 糜蛋白酶可显著减弱L - NAME不敏感舒张的幅度。这些结果表明,至少有两种神经递质,可能是NO或含NO的化合物以及VIP,参与气道中的i - NANC传递。在膀胱中,对盆神经刺激会出现一个大的、短暂的阿托品抵抗性收缩。这被α,β - 亚甲基ATP阻断,表明它是由ATP引起的。没有抑制性神经支配的证据。在尿道,收缩完全被阿托品和胍乙啶阻断;一种快速的NANC舒张被阻断NO合成的药物消除。含有肽类的神经支配尿道和膀胱,也可能参与其中。这些结果表明,所有内脏平滑肌可能都接受涉及NO的抑制性NANC神经支配。ATP可使膀胱收缩,但使消化道舒张。肽类的作用尚不清楚,但有证据表明在许多器官中P物质可能是一种兴奋性递质,而VIP是一种抑制性递质。