Stephens R L, Ishikawa T, Weiner H, Novin D, Taché Y
Center for Ulcer Research and Education, Veterans Administration Wadsworth Medical Center, Los Angeles, California.
Am J Physiol. 1988 May;254(5 Pt 1):G639-43. doi: 10.1152/ajpgi.1988.254.5.G639.
Medullary sites inducing gastric acid secretion in response to microinjection of the stable analogue of thyrotropin-releasing hormone (TRH; RX 77368, pGlu-His-[3,3'-dimethyl]-Pro-NH2) were investigated in urethan-anesthetized rats. Gastric acid output was recorded every 2 min through a double gastric cannula constantly perfused with 0.9% saline solution maintained at pH 5.5 using an automatic titrator. Unilateral microinjection of RX 77368 (10-100 ng in 50-nl volume) into the dorsal vagal complex (DVC), the dorsal vagal nucleus and nucleus tractus solitarius, induced a significant dose-dependent stimulation of gastric acid secretion. The peak response occurred within 50 min and lasted over 1 h. Other medullary sites, including the lateral, dorsal, and parvocellular reticular nuclei; the medial longitudinal fasciculus; and the medial cuneate nucleus injected with RX 77368 (10-100 ng), were inactive. The TRH metabolites, TRH-OH and His-Pro diketopiperazine (100 ng), injected into the DVC did not influence gastric acid secretion. The stimulation of gastric acid secretion induced by DVC injection of TRH was abolished by vagotomy. These results demonstrate that 1) the DVC is an important site of action for TRH-induced stimulation of gastric acid secretion, 2) TRH action in the DVC is not secondary to the formation of TRH metabolites, and 3) the effect is expressed by vagal efferent pathways. These findings added to the high concentration of TRH-immunoreactivity and receptors in the DVC suggest a role for endogenous TRH in the regulation of vagal outflow to the stomach.
在乌拉坦麻醉的大鼠中，研究了经微量注射促甲状腺激素释放激素（TRH；RX 77368，焦谷氨酸-组氨酸-[3,3'-二甲基]-脯氨酰胺）后诱导胃酸分泌的延髓部位。通过双胃插管每2分钟记录一次胃酸分泌量，该插管持续灌注用自动滴定仪维持在pH 5.5的0.9%盐溶液。向迷走神经背侧复合体（DVC）、迷走神经背核和孤束核单侧微量注射RX 77368（50 nl体积中含10 - 100 ng），可引起胃酸分泌显著的剂量依赖性刺激。峰值反应在50分钟内出现，并持续超过1小时。向其他延髓部位，包括外侧、背侧和小细胞网状核、内侧纵束和内侧楔束核注射RX 77368（10 - 100 ng）均无活性。向DVC注射TRH的代谢产物TRH - OH和组氨酸-脯氨酸二酮哌嗪（100 ng）不影响胃酸分泌。切断迷走神经可消除DVC注射TRH所诱导的胃酸分泌刺激。这些结果表明：1）DVC是TRH诱导胃酸分泌刺激的重要作用部位；2）TRH在DVC中的作用并非继发于TRH代谢产物的形成；3）该效应通过迷走神经传出通路表达。这些发现加上DVC中高浓度的TRH免疫反应性和受体，提示内源性TRH在调节迷走神经向胃的传出中起作用。
