Guidobono F, Netti C, Pecile A, Zanelli J M, Gaines-Das R E
Università degli Studi, Dipartimento di Farmacologia, Milano, Italy.
Pharmacol Res. 1990 May-Jun;22(3):287-95. doi: 10.1016/1043-6618(90)90726-t.
It is well established that salmon calcitonin (sCT), given either by central (intracerebroventricular) or peripheral (parenteral) injection is a potent inhibitor of gastric acid secretion. It is generally believed that this effect of sCT is mediated by the central nervous system based on reports that the effective peripheral dose is up to 1000 times greater than the effective dose administered centrally. We have reexamined this hypothesis by carrying out a number of independent experiments in two laboratories on the effect of sCT, given either by intracerebroventricular or by subcutaneous injection, on basal gastric acid secretion in unanaesthetized rats. Statistical evaluation of the data showed the reproducibility of the effective inhibitory dose ranges of sCT despite the inherent variability of the pylorus ligated rat system (Shay test). The effective dose range for sCT given centrally was between three- and ten-fold lower than that for peripherally administered sCT. There is no published evidence that a significant amount of peripherally administered sCT passes through the blood-brain barrier to relevant areas of the brain and this is confirmed in our study by autoradiography of serial sections of brain following intravenous administration of radioiodinated sCT. It therefore appears that the inhibitory effect of sCT, given centrally or peripherally, may not necessarily be mediated by a common pathway in the central nervous system. Our results also show that the inhibitory effect of peripherally administered sCT is lost when rats are treated with cysteamine to deplete somatostatin, thus implicating somatostatin as a peripheral mediator.
现已充分证实，通过中枢（脑室内）或外周（胃肠外）注射给予鲑鱼降钙素（sCT）是胃酸分泌的强效抑制剂。基于有效外周剂量比中枢给药有效剂量高达1000倍的报道，一般认为sCT的这种作用是由中枢神经系统介导的。我们通过在两个实验室进行多项独立实验，重新审视了这一假设，实验内容是脑室内或皮下注射sCT对未麻醉大鼠基础胃酸分泌的影响。对数据的统计评估表明，尽管幽门结扎大鼠系统（ Shay试验）存在固有变异性，但sCT有效抑制剂量范围具有可重复性。中枢给予sCT的有效剂量范围比外周给予sCT的有效剂量范围低三至十倍。没有已发表的证据表明大量外周给予的sCT穿过血脑屏障到达大脑的相关区域，我们的研究通过静脉注射放射性碘标记的sCT后对脑连续切片进行放射自显影证实了这一点。因此，似乎中枢或外周给予sCT的抑制作用不一定由中枢神经系统中的共同途径介导。我们的结果还表明，用半胱胺处理大鼠以耗尽生长抑素后，外周给予sCT的抑制作用消失，从而表明生长抑素是一种外周介质。
