Persson K, Garcia-Pascual A, Andersson K E
Department of Clinical Pharmacology, University Hospital of Lund, Sweden.
Acta Physiol Scand. 1991 Sep;143(1):45-53. doi: 10.1111/j.1748-1716.1991.tb09200.x.
Calcitonin gene-related peptide has been demonstrated in urinary bladder nerves, and suggested to play a role in local control of bladder motility. In isolated strips of pig detrusor muscle, calcitonin gene-related peptide did not affect spontaneous contractile activity, or contractions induced by high K+, carbachol, substance P, and electrical field stimulation. In contrast, calcitonin gene-related peptide elicited a concentration-dependent and pronounced (78-99%) relaxation of vesical arteries precontracted with endothelin-1, noradrenaline or prostaglandin F2 alpha. As a vasodilator, CGRP was approximately 50 times more potent than acetylcholine. Removal of the endothelium abolished acetylcholine-induced relaxation, but did not affect the relaxation produced by calcitonin gene-related peptide. Pretreatment with methylene blue, glibenclamide or indomethacin had no influence on CGRP's ability to relax the vessels. The inhibitor of NO-synthesis, NG-nitro-L-arginine, had no effect on the maximum vascular relaxation induced by calcitonin gene-relate peptide. It is concluded that in the pig, calcitonin gene-related peptide has no functionally important mechanical effects on isolated detrusor muscle strips, but is a potent dilator of vesical arteries. The vascular effects of the peptide are endothelium-independent, and seem to be exerted directly on the vascular smooth muscle.
降钙素基因相关肽已在膀胱神经中得到证实,并被认为在膀胱运动的局部控制中发挥作用。在猪逼尿肌的离体条带中,降钙素基因相关肽不影响自发收缩活动,也不影响由高钾、卡巴胆碱、P物质和电场刺激诱导的收缩。相反,降钙素基因相关肽能使预先用内皮素-1、去甲肾上腺素或前列腺素F2α预收缩的膀胱动脉产生浓度依赖性且显著的(78 - 99%)舒张。作为一种血管舒张剂,降钙素基因相关肽的效力约为乙酰胆碱的50倍。去除内皮可消除乙酰胆碱诱导的舒张,但不影响降钙素基因相关肽产生的舒张。用亚甲蓝、格列本脲或吲哚美辛预处理对降钙素基因相关肽舒张血管的能力没有影响。一氧化氮合成抑制剂NG-硝基-L-精氨酸对降钙素基因相关肽诱导的最大血管舒张没有影响。结论是,在猪中,降钙素基因相关肽对离体逼尿肌条带没有功能上重要的机械作用,但它是膀胱动脉的一种强效舒张剂。该肽的血管作用不依赖于内皮,似乎直接作用于血管平滑肌。