Inhibitory effects of endogenous dopaminergic neurotoxin, norsalsolinol on dopamine secretion in PC12 rat pheochromocytoma cells.

Abstract

Naturally occurring neurotoxins, 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines (DHTIQs), thought to be the causative agents of Parkinsonism. DHTIQs including norsalsolinol have been found in the mammalian central nervous system. Norsalsolinol can be formed by a non-enzymatic Pictet-Spengler condensation reaction between dopamine and formaldehyde, and has been detected in the urine of Parkinsonian patients. However, the effects of DHTIQs on the secretion of dopamine, as well as other neurotransmitters, are not well understood. This study investigated the effects of norsalsolinol on dopamine secretion from nerve growth factor-differentiated PC12 cells. Norsalsolinol (1-100 microM) pretreatment suppressed both ATP (100 microM)- and K(+) (50 mM)-induced dopamine secretion from PC12 cells in a concentration-dependent fashion, but did not affect basal dopamine secretion. In beta-escin-permeabilized PC12 cells, norsalsolinol pretreatment suppressed Ca(2+) (pCa=4-8)-induced dopamine secretion, but did not inhibit the secretagogue-induced change in intracellular Ca(2+) concentration. These results suggest that norsalsolinol causes the inhibition of secretagogue-induced dopamine secretion from PC12 cells without altering intracellular Ca(2+) concentration. Inhibition of dopamine secretion by norsalsolinol may also be involved in postural abnormality in Parkinson's disease.

• Authors: Y Maruyama, H Teraoka, H Iwata, A Kazusaka, S Fujita
• Journal: Neurochemistry international (Neurochem Int) Vol. 38 Issue 7 Pg. 567-72 (Jun 2001) ISSN: 0197-0186 [Print] England
• PMID: 11290381 (Publication Type: Journal Article)

Chemical References

• Dopamine Antagonists
• Salsoline Alkaloids
• norsalsolinol
• Calcium
• Dopamine

Topics

• Animals
• Calcium (metabolism)
• Dopamine (metabolism)
• Dopamine Antagonists (pharmacology)
• Ion Transport
• PC12 Cells
• Pheochromocytoma (metabolism, pathology)
• Rats
• Salsoline Alkaloids (pharmacology)