Pancreatic acinar cells utilize tyrosine to synthesize L-dihydroxyphenylalanine

Exp Biol Med (Maywood). 2021 Dec;246(23):2533-2542. doi: 10.1177/15353702211032552. Epub 2021 Jul 27.

Abstract

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 in vivo 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.

Keywords: L-DOPA; Pancreatic acinar cells; dopamine; pancreatic juice; physiology; tyrosine hydroxylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinar Cells / metabolism*
  • Animals
  • Aromatic Amino Acid Decarboxylase Inhibitors / pharmacology
  • Aromatic-L-Amino-Acid Decarboxylases / immunology
  • Aromatic-L-Amino-Acid Decarboxylases / metabolism
  • Atropine / pharmacology
  • Bethanechol / pharmacology
  • Cell Line
  • Dihydroxyphenylalanine / analysis
  • Dihydroxyphenylalanine / biosynthesis*
  • Dopamine / analysis
  • Dopamine / biosynthesis*
  • Hydrazines / pharmacology
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Tyrosine / metabolism*
  • Tyrosine 3-Monooxygenase / antagonists & inhibitors
  • Tyrosine 3-Monooxygenase / immunology
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Aromatic Amino Acid Decarboxylase Inhibitors
  • Hydrazines
  • Bethanechol
  • Tyrosine
  • Dihydroxyphenylalanine
  • Atropine
  • 3-hydroxybenzylhydrazine
  • Tyrosine 3-Monooxygenase
  • Aromatic-L-Amino-Acid Decarboxylases
  • Dopamine