Iwatsuki K, Horiuchi A, Ren L M, Chiba S
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Eur J Pharmacol. 1993 Nov 2;249(1):19-24. doi: 10.1016/0014-2999(93)90657-4.
The effects of KRN2391, a newly synthesized vasodilator, on pancreatic exocrine secretion in anesthetized dogs were compared with those of Ki3315, pinacidil and nitroprusside. Graded doses of KRN2391 (0.03-3 mumol/kg) and nitroprusside (0.003-0.3 mumol/kg) injected i.a. produced dose-dependent increases in the secretion of pancreatic juice, with a high concentration of protein and low concentration of bicarbonate, but Ki3315 or pinacidil did not (up to 10 mumol/kg). KRN2391 and nitroprusside increased the cyclic GMP levels in pancreatic tissue together with the increase in pancreatic secretion. Methylene blue decreased pancreatic secretion and cyclic GMP levels stimulated by KRN2391 and nitroprusside, but glibenclamide did not. KRN2391, Ki3315, pinacidil and nitroprusside caused vasodilator actions. These results suggest that KRN2391 has direct secretory properties on pancreatic exocrine glands of the dog and its nitro moiety has an important role in the stimulation of pancreatic secretion, but the K+ channel opening action or increasing of blood flow rate does not participate in the secretion.
将新合成的血管扩张剂KRN2391对麻醉犬胰腺外分泌的影响与Ki3315、吡那地尔和硝普钠进行了比较。经腹腔注射不同剂量的KRN2391（0.03 - 3 μmol/kg）和硝普钠（0.003 - 0.3 μmol/kg）可使胰液分泌呈剂量依赖性增加，胰液中蛋白质浓度高而碳酸氢盐浓度低，但Ki3315或吡那地尔（高达10 μmol/kg）则无此作用。KRN2391和硝普钠在增加胰腺分泌的同时，可提高胰腺组织中的环鸟苷酸水平。亚甲蓝可降低KRN2391和硝普钠刺激引起的胰腺分泌及环鸟苷酸水平，但格列本脲则无此作用。KRN2391、Ki3315、吡那地尔和硝普钠均具有血管舒张作用。这些结果表明，KRN2391对犬胰腺外分泌腺具有直接分泌特性，其硝基部分在刺激胰腺分泌中起重要作用，但钾通道开放作用或血流速度增加并不参与该分泌过程。
