Rothstein R D, Johnson E, Ouyang A
Department of Medicine, University of Pennsylvania, Hospital of University of Pennsylvania, Philadelphia 19104.
Am J Physiol. 1989 Sep;257(3 Pt 1):G447-53. doi: 10.1152/ajpgi.1989.257.3.G447.
The purpose of this study was to determine the mechanism of action of substance P at the distal ileum, ileocecal sphincter (ICS), and proximal colon in the cat and to determine the localization of substance P receptors at these sites by autoradiography. Intraluminal pressures and myoelectric activity were recorded at the feline distal ileum, ICS, and colon. Substance P caused a tonic and phasic spike-dependent contractile response at all three sites. The antagonists propranolol, phentolamine, and naloxone did not affect the contractile response to substance P at the ileum, ICS, or colon. The ganglionic blocker trimethaphan camsylate potentiated the response to substance P at all three sites, P less than 0.05. Both atropine and tetrodotoxin reduced the response of substance P at the ileal site. At the ICS, atropine or tetrodotoxin reduced, but did not obliterate, the effect of substance P. Neither atropine nor tetrodotoxin reduced substance P-induced colonic contractions. By use of autoradiography, specific binding for substance P was determined to be present at all three sites with the greatest concentration of substance P receptors in the circular muscle layer. In conclusion, these studies suggest multiple sites of action of substance P. At the ileum, substance P causes contraction via a cholinergic pathway. At the ICS, substance P has an excitatory action through a cholinergic pathway and also at smooth muscle receptors. In the proximal colon, the excitatory action of substance P is via smooth muscle receptors. An inhibitory ganglionic pathway also exists at all three sites. Substance P receptors exist predominantly in the circular muscle region of the ileum, ICS, and the proximal colon.
本研究的目的是确定P物质在猫的回肠末端、回盲括约肌（ICS）和结肠近端的作用机制，并通过放射自显影确定这些部位P物质受体的定位。记录了猫回肠末端、ICS和结肠的腔内压力和肌电活动。P物质在所有三个部位均引起了强直和相位性的依赖于锋电位的收缩反应。拮抗剂普萘洛尔、酚妥拉明和纳洛酮对回肠、ICS或结肠对P物质的收缩反应均无影响。神经节阻滞剂樟磺咪芬在所有三个部位均增强了对P物质的反应，P<0.05。阿托品和河豚毒素均降低了回肠部位对P物质的反应。在ICS处，阿托品或河豚毒素降低了但并未消除P物质的作用。阿托品和河豚毒素均未降低P物质引起的结肠收缩。通过放射自显影，确定在所有三个部位均存在P物质的特异性结合，其中环形肌层中P物质受体的浓度最高。总之，这些研究表明P物质有多个作用位点。在回肠，P物质通过胆碱能途径引起收缩。在ICS，P物质通过胆碱能途径以及平滑肌受体产生兴奋作用。在结肠近端，P物质的兴奋作用是通过平滑肌受体。在所有三个部位也存在抑制性神经节途径。P物质受体主要存在于回肠、ICS和结肠近端的环形肌区域。
