Halter F, Witzel L, Kohler B, Hadorn B
Scand J Gastroenterol. 1975;10(1):81-5.
In an informative qualitative study 75 U (near the range of 1 U/kg) secretin given as a snuff resulted in a weak but significant stimulation of pancreatic bicarbonate output in 8 volunteers studied. The result further indicated that this dose would slightly inhibit pentagastrin-stimulated gastric acid secretion. This was confirmed in a quantitative study at the dose of 150 U (similar to 2 U/kg), and the mean amount of inhibition of MAO was 30% in the 10 subjects studied. A supramaximal dose of 1 mg (approximatively 54 U/kg) of synthetic secretin given to one volunteer resulted in a transient block of near maximally pentagastrin-stimulated gastric acid secretion. The amount of acid inhibition as compared to a control experiment was 45% in the first and 52% in the two post-secretin hours. These results indicate that secretin given as a snuff at dose levels that would induce maximal pancreatic secretion when given as an i.v. injection results only in a weak inhibition of stimulated gastric acid secretion and evokes only a little stimulation of pancreatic bicarbonate secretion. Supramaximal secretin snuff doses have, however, a potent effect on both gastric and pancreatic secretion that is of similar order to that achieved by intravenous secretin. Owing to the obviously incomplete absorption of secretin through the nasal mucosa, secretin snuff is unlikely to solve the therapeutic problem of duodenal ulcer disease. If, however, an active fragment of the peptide could be synthetized at a reasonable price, the greater convenience of pernasal application might compensate for the partial loss of action.
在一项信息丰富的定性研究中,给8名志愿者吸入75单位(接近1单位/千克的范围)的促胰液素,结果导致胰腺碳酸氢盐分泌受到微弱但显著的刺激。结果还表明,该剂量会轻微抑制五肽胃泌素刺激的胃酸分泌。在一项定量研究中,以150单位(类似于2单位/千克)的剂量证实了这一点,在研究的10名受试者中,最大酸排量(MAO)的平均抑制量为30%。给一名志愿者注射1毫克(约54单位/千克)的合成促胰液素超最大剂量,导致近乎最大程度的五肽胃泌素刺激的胃酸分泌出现短暂阻断。与对照实验相比,在注射促胰液素后的第一个小时,酸抑制量为45%,在随后的两个小时为52%。这些结果表明,以鼻烟形式给予促胰液素,其剂量在静脉注射时会诱导最大胰腺分泌,但只会导致刺激胃酸分泌的微弱抑制,并且只会引起胰腺碳酸氢盐分泌的轻微刺激。然而,超最大剂量的促胰液素鼻烟对胃和胰腺分泌都有强效作用,其程度与静脉注射促胰液素所达到的程度相似。由于促胰液素通过鼻黏膜的吸收明显不完全,促胰液素鼻烟不太可能解决十二指肠溃疡疾病的治疗问题。然而,如果能够以合理的价格合成该肽的活性片段,经鼻应用的更大便利性可能会弥补部分作用丧失的问题。