Lecci A, Altamura M, Capriati A, Maggi C A
Clinical Research Department, Menarini Ricerche, Florence, Italy.
Eur Rev Med Pharmacol Sci. 2008 Aug;12 Suppl 1:69-80.
Peptides of the tachykinin (TK) family were first discovered in the gastrointestinal tissue about 75 years ago and supposed to be involved in gastrointestinal (GI) motility. This hypothesis has been repeatedly proven, although the role of TKs on motility is modulatory rather than pivotal. Furthermore, beyond the well known excitatory role, it has been acknowledged that TKs can also inhibit GI motility. TKs act at 3 receptors termed as TK NK1 (NK1r), NK2 (NK2r), and NK3 (NK3r) receptors. The view gained through intense preclinical research suggested that motor effects induced by the stimulation of NK2r were prominently mediated by a direct action on smooth muscle, those produced by the stimulation of NK1r were due to both muscular and neuronal effects, whereas the motor effects induced by NK3r were exclusively mediated by neuronal effects. Recent functional and anatomical findings in humans are challenging this concept since NK2r have been found in several kinds of myenteric neurons and selective NK2r antagonists can, in particular conditions, produce GI motor effects likely related to a neuronal site of action. Furthermore, the evidence for a myotropic role of NK1r is scarce, and very few studies, if any, have documented a functional role for NK3r. The findings that an acute or a long lasting blockade of NK2r does not alter normal GI functions and that these receptors can modulate visceral sensitivity are good starting points for testing this class of drugs in GI diseases characterised by altered GI motility.
速激肽（TK）家族的肽类大约在75年前首次在胃肠道组织中被发现，并被认为与胃肠（GI）蠕动有关。尽管速激肽对蠕动的作用是调节性而非关键性的，但这一假设已被反复证实。此外，除了众所周知的兴奋作用外，人们还认识到速激肽也能抑制胃肠蠕动。速激肽作用于3种受体，分别称为TK NK1（NK1r）、NK2（NK2r）和NK3（NK3r）受体。通过深入的临床前研究得出的观点表明，刺激NK2r所诱导的运动效应主要是通过对平滑肌的直接作用介导的，刺激NK1r所产生的运动效应是由肌肉和神经元效应共同导致的，而NK3r所诱导的运动效应则完全由神经元效应介导。最近在人体中的功能和解剖学研究结果对这一概念提出了挑战，因为在几种肌间神经元中发现了NK2r，并且在特定条件下，选择性NK2r拮抗剂可产生可能与神经元作用部位相关的胃肠运动效应。此外，NK1r具有肌otropic作用的证据很少，而且几乎没有研究记录过NK3r的功能作用。NK2r的急性或长期阻断不会改变正常胃肠功能以及这些受体可调节内脏敏感性的研究结果，是在以胃肠蠕动改变为特征的胃肠疾病中测试这类药物的良好起点。
