Malis D D, Rist B, Nicoucar K, Beck-Sickinger A G, Morel D R, Lacroix J S
Laboratory of Experimental Rhinology, Clinic of Otorhinolaryngology, University Hospital, CH-1211, Geneva, Switzerland.
Regul Pept. 2001 Sep 15;101(1-3):101-8. doi: 10.1016/s0167-0115(01)00275-0.
Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide and potent vasodilatator agent located in sensory C fibres. Several functional studies suggest that CGRP could be involved in the vasodilatation of different vascular beds during neurogenic inflammation. We have studied, in pentobarbital anaesthetised pigs, the antagonistic effect of local intra-arterial (i.a.) pretreatment with the analogues CGRP 8-37, [D31, P34, F35]CGRP 27-37 and [N31, P34, F35]CGRP 27-37 on the vasodilatation of the nasal vascular bed induced by exogenous CGRP, capsaicin, bradykinin (BK) and histamine. The attenuating effect of CGRP 8-37 analogue on exogenous CGRP-induced vasodilatation, previously described in other in vivo animal models, was confirmed in the pig nasal mucosa. It also interfered with BK-and, to a lesser extent, with capsaicin-and histamine-induced decrease in vascular resistance. CGRP 27-37 analogues reduced the duration of CGRP-, capsaicin- and BK-induced vasodilatation by more than 50%. Peak values of vasodilatation were attenuated by more than 25% overall. Attenuation of histamine-induced decrease in vascular resistance was less pronounced. It is concluded that CGRP 27-37 analogues antagonise the action of exogenous CGRP, capsaicin, BK and histamine by attenuating their vasodilatation effect, both in intensity and duration. These results strongly suggest that BK- and histamine-induced vasodilatation is partly mediated by CGRP. CGRP 8-37 and 27-37 appear to be potential contributors to the study of CGRP and its physiological role in neurogenic inflammation. In addition, they may have putative therapeutic applications in the treatment of rhinitic patients suffering from chronic nasal obstruction.
降钙素基因相关肽（CGRP）是一种由37个氨基酸组成的肽，是位于感觉C纤维中的强效血管舒张剂。多项功能研究表明，CGRP可能参与神经源性炎症期间不同血管床的血管舒张。我们在戊巴比妥麻醉的猪身上研究了局部动脉内（i.a.）预先用类似物CGRP 8-37、[D31，P34，F35]CGRP 27-37和[N31，P34，F35]CGRP 27-37预处理对外源性CGRP、辣椒素、缓激肽（BK）和组胺诱导的鼻血管床血管舒张的拮抗作用。CGRP 8-37类似物对外源性CGRP诱导的血管舒张的减弱作用，先前在其他体内动物模型中已有描述，在猪鼻黏膜中得到了证实。它还干扰了BK诱导的血管舒张，对辣椒素和组胺诱导的血管阻力降低的干扰程度较小。CGRP 27-37类似物使CGRP、辣椒素和BK诱导的血管舒张持续时间缩短了50%以上。血管舒张的峰值总体上减弱了25%以上。组胺诱导的血管阻力降低的减弱不太明显。得出的结论是，CGRP 27-37类似物通过减弱外源性CGRP、辣椒素、BK和组胺的血管舒张作用，在强度和持续时间上拮抗它们的作用。这些结果强烈表明，BK和组胺诱导的血管舒张部分是由CGRP介导的。CGRP 8-37和27-37似乎是研究CGRP及其在神经源性炎症中的生理作用的潜在因素。此外，它们可能在治疗患有慢性鼻塞的鼻炎患者方面具有潜在的治疗应用。
