Nurko S, Dunn B M, Rattan S
Harvard Digestive Diseases Center, Thorndike Laboratory, Charles A. Dana Research Institute, Division of Gastroenterology, Beth Israel Hospital, Boston, Massachusetts.
Gastroenterology. 1989 Feb;96(2 Pt 1):403-13. doi: 10.1016/0016-5085(89)91564-3.
The purpose of this investigation was to characterize the nature of peptide histidine isoleucine (PHI) and vasoactive intestinal polypeptide (VIP) receptors, and to examine the role of PHI in internal anal sphincter (IAS) relaxation. The studies were performed on opossums anesthetized with alpha-chloralose. The pressures in the IAS were recorded using continuously perfused catheters. The IAS responses to PHI analogues, PHI-27, PHM-27, PHI-(14-27)-NH2, PHI-(1-13), to VIP, to rectal balloon distention, sacral nerve stimulation, and local intramural stimulation were evaluated before and after PHI-(14-27)-NH2, PHI tachyphylaxis, and the VIP antagonists [4 Cl-D-Phe6, Leu17] VIP (VIP analogue) and (N-Ac-Tyr1, D-Phe2)-GRF(1-29)-NH2 (growth hormone releasing factor analogue). The inhibitory responses by all of the PHI analogues and VIP were not modified by tetrodotoxin. PHI-(14-27)-NH2 and PHI tachyphylaxis caused significant antagonism of the fall in internal anal sphincter pressure by PHI-27 and PHM-27 without modifying the IAS responses to VIP and rectal balloon distention, sacral nerve stimulation, and local intramural stimulation. On the other hand, VIP and growth hormone releasing factor analogues caused significant antagonism of VIP responses without modifying the responses to PHI-27. We conclude that distinct PHI and VIP receptors are present in the IAS smooth muscle and that PHI may not play a significant role in the IAS relaxation via the rectoanal reflex.
本研究的目的是表征肽组氨酸异亮氨酸（PHI）和血管活性肠肽（VIP）受体的性质，并研究PHI在肛门内括约肌（IAS）松弛中的作用。研究在使用α-氯醛糖麻醉的负鼠身上进行。使用连续灌注导管记录IAS中的压力。在给予PHI-（14-27）-NH2、PHI快速耐受性以及VIP拮抗剂[4 Cl-D-Phe6，Leu17] VIP（VIP类似物）和（N-Ac-Tyr1，D-Phe2）-GRF（1-29）-NH2（生长激素释放因子类似物）之前和之后，评估IAS对PHI类似物、PHI-27、PHM-27、PHI-（14-27）-NH2、PHI-（1-13）、对VIP、对直肠球囊扩张、骶神经刺激和局部壁内刺激的反应。所有PHI类似物和VIP的抑制反应均未被河豚毒素改变。PHI-（14-27）-NH2和PHI快速耐受性导致PHI-27和PHM-27引起的肛门内括约肌压力下降出现显著拮抗作用，而不改变IAS对VIP、直肠球囊扩张、骶神经刺激和局部壁内刺激的反应。另一方面，VIP和生长激素释放因子类似物导致VIP反应出现显著拮抗作用，而不改变对PHI-27的反应。我们得出结论，IAS平滑肌中存在不同的PHI和VIP受体，并且PHI可能在通过直肠肛门反射的IAS松弛中不发挥重要作用。
