Department of Physiology and Pathophysiology, School of Basic Medical Science, Capital Medical University, Beijing 100069, China.
Grade 2017 Clinical Medicine, the Sixth Clinical School of Capital Medical University, Beijing 100029, China.
Exp Biol Med (Maywood). 2021 Dec;246(23):2533-2542. doi: 10.1177/15353702211032552. Epub 2021 Jul 27.
The pancreatic β cells can synthesize dopamine by taking L-dihydroxyphenylalanine, but whether pancreatic acinar cells synthesize dopamine has not been confirmed. By means of immunofluorescence, the tyrosine hydroxylase -immunoreactivity and aromatic amino acid decarboxylase (AADC)- immunoreactivity were respectively observed in pancreatic acinar cells and islet β cells. Treatment with L-dihydroxyphenylalanine, not tyrosine, caused the production of dopamine in the incubation of INS-1 cells (rat islet β cell line) and primary isolated islets, which was blocked by AADC inhibitor NSD-1015. However, only L-dihydroxyphenylalanine, but not dopamine, was detected when AR42J cells (rat pancreatic acinar cell line) were treated with tyrosine, which was blocked by tyrosine hydroxylase inhibitor AMPT. Dopamine was detected in the coculture of INS-1 cells with AR42J cells after treatment with tyrosine. In an study, pancreatic juice contained high levels of L-dihydroxyphenylalanine and dopamine. Both L-dihydroxyphenylalanine and dopamine accompanied with pancreatic enzymes and insulin in the pancreatic juice were all significantly increased after intraperitoneal injection of bethanechol chloride and their increases were all blocked by atropine. Inhibiting TH with AMPT blocked bethanechol chloride-induced increases in L-dihydroxyphenylalanine and dopamine, while inhibiting AADC with NSD-1015 only blocked the dopamine increase. Bilateral subdiaphragmatic vagotomy of rats leads to significant decreases of L-dihydroxyphenylalanine and dopamine in pancreatic juice. These results suggested that pancreatic acinar cells could utilize tyrosine to synthesize L-dihydroxyphenylalanine, not dopamine. Islet β cells only used L-dihydroxyphenylalanine, not tyrosine, to synthesize dopamine. Both L-dihydroxyphenylalanine and dopamine were respectively released into the pancreatic duct, which was regulated by the vagal cholinergic pathway. The present study provides important evidences for the source of L-dihydroxyphenylalanine and dopamine in the pancreas.
胰岛β细胞可以通过摄取 L-二羟苯丙氨酸合成多巴胺,但胰腺腺泡细胞是否合成多巴胺尚未得到证实。通过免疫荧光技术,分别观察到了胰腺腺泡细胞和胰岛β细胞中的酪氨酸羟化酶免疫反应性和芳香族氨基酸脱羧酶(AADC)免疫反应性。在 INS-1 细胞(大鼠胰岛β细胞系)和原代分离胰岛的孵育中,L-二羟苯丙氨酸而非酪氨酸的处理导致多巴胺的产生,而 AADC 抑制剂 NSD-1015 则阻断了这种作用。然而,当用酪氨酸处理 AR42J 细胞(大鼠胰腺腺泡细胞系)时,只检测到 L-二羟苯丙氨酸,而不是多巴胺,而酪氨酸羟化酶抑制剂 AMPT 则阻断了这种作用。在用酪氨酸处理后,在 INS-1 细胞与 AR42J 细胞的共培养物中检测到多巴胺。在一项研究中,胰腺液中含有高水平的 L-二羟苯丙氨酸和多巴胺。在腹腔内注射氨甲酰胆碱后,胰液中的 L-二羟苯丙氨酸和多巴胺与胰腺酶和胰岛素一起显著增加,而阿托品则阻断了它们的增加。用 AMPT 抑制 TH 阻断了氨甲酰胆碱诱导的 L-二羟苯丙氨酸和多巴胺的增加,而用 NSD-1015 抑制 AADC 仅阻断了多巴胺的增加。大鼠双侧膈下迷走神经切断术导致胰腺液中 L-二羟苯丙氨酸和多巴胺的显著减少。这些结果表明,胰腺腺泡细胞可以利用酪氨酸合成 L-二羟苯丙氨酸,而不是多巴胺。胰岛β细胞仅利用 L-二羟苯丙氨酸,而不是酪氨酸,来合成多巴胺。L-二羟苯丙氨酸和多巴胺分别被释放到胰腺导管中,这受迷走神经胆碱能途径的调节。本研究为胰腺中 L-二羟苯丙氨酸和多巴胺的来源提供了重要证据。