Iwatsuki K, Ren L M, Chiba S
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Eur J Pharmacol. 1992 Aug 6;218(2-3):237-41. doi: 10.1016/0014-2999(92)90174-3.
The effects of YM435, a novel dopamine (DA) D1 receptor agonist, on pancreatic exocrine secretion were investigated in anesthetized dogs. Each drug was injected i.a. as a single bolus. Graded doses of YM435 (0.3-30 nmol) produced dose-dependent increases in the rate of secretion of pancreatic juice, with a maximum effect at approximately 10 nmol, and with a high concentration of bicarbonate and low concentration of protein. SCH23390 (3-30 nmol), a selective D1 receptor antagonist, caused a progressive parallel shift to the right of the dose-response curve for YM435-stimulated pancreatic secretion without changing the maximum response. Schild analysis of the data indicated that the inhibitory constant (Ki) value was 2.9 nmol, and that SCH23390 inhibited YM435-stimulated pancreatic secretion in a competitive manner. Both DA (0.01-3 mumol) and SKF38393 (0.3-30 mumol), a selective D1 receptor agonist, also increased the secretory rate and bicarbonate concentration, and decreased the protein concentration to the same extent as YM435. These results suggest that YM435 is a potent stimulant of pancreatic exocrine secretion by acting on DA D1 receptors of the pancreas in dogs.
在麻醉犬中研究了新型多巴胺（DA）D1受体激动剂YM435对胰腺外分泌的影响。每种药物均腹腔内注射，作为单次推注。不同剂量的YM435（0.3 - 30 nmol）可使胰液分泌速率呈剂量依赖性增加，在约10 nmol时达到最大效应，且胰液中碳酸氢盐浓度高而蛋白质浓度低。选择性D1受体拮抗剂SCH23390（3 - 30 nmol）使YM435刺激的胰腺分泌剂量反应曲线逐渐平行右移，而最大反应不变。对数据进行Schild分析表明，抑制常数（Ki）值为2.9 nmol，且SCH23390以竞争性方式抑制YM435刺激的胰腺分泌。多巴胺（0.01 - 3 μmol）和选择性D1受体激动剂SKF38393（0.3 - 30 μmol）也能增加分泌速率和碳酸氢盐浓度，并使蛋白质浓度降低至与YM435相同的程度。这些结果表明，YM435通过作用于犬胰腺的DA D1受体，是胰腺外分泌的强效刺激剂。
