Reasbeck P G, Burns S M, Shulkes A
Department of Surgery, University of Queensland, Brisbane, Australia.
Gastroenterology. 1988 Oct;95(4):966-71. doi: 10.1016/0016-5085(88)90170-9.
We have measured the effects of intravenous infusion of calcitonin gene-related peptide at doses of 2.5, 10, and 50 pmol/kg.min on net jejunal water and solute fluxes and on plasma somatostatin concentrations in dogs. The hemodynamic effects and the pharmacokinetics of the peptide were also assessed. Using the triple-lumen perfusion technique in unsedated restrained animals it was shown that the highest dose of the peptide stimulated a transient net jejunal water and electrolyte secretion, and induced diarrhea in 4 of 6 animals receiving it. The peptide also induced dose-dependent tachycardia, hypotension, and increases in plasma immunoreactive somatostatin. All three doses of calcitonin gene-related peptide produced plasma immunoreactive peptide levels within the elevated range previously measured in human patients with medullary thyroid carcinoma. Calcitonin gene-related peptide may have a major role in the pathogenesis of secretory diarrhea in medullary thyroid carcinoma.
我们已测定了以2.5、10和50皮摩尔/千克·分钟的剂量静脉输注降钙素基因相关肽对犬空肠净水和溶质通量以及血浆生长抑素浓度的影响。还评估了该肽的血流动力学效应和药代动力学。在未镇静的受限动物中使用三腔灌注技术表明，最高剂量的该肽刺激了短暂的空肠净水和电解质分泌，并在接受该剂量的6只动物中有4只诱发了腹泻。该肽还诱发了剂量依赖性心动过速、低血压以及血浆免疫反应性生长抑素升高。所有三种剂量的降钙素基因相关肽产生的血浆免疫反应性肽水平均在先前在甲状腺髓样癌患者中测得的升高范围内。降钙素基因相关肽可能在甲状腺髓样癌分泌性腹泻的发病机制中起主要作用。
