Cardiovascular actions of DOPA mediated by the gene product of ocular albinism 1

J Pharmacol Sci. 2014;126(1):14-20. doi: 10.1254/jphs.14r03cr. Epub 2014 Sep 4.

Abstract

l-3,4-Dihydroxyphenylalanine (DOPA) is the metabolic precursor of dopamine, and the single most effective agent in the treatment of Parkinson's disease. One problem with DOPA therapy for Parkinson's disease is its cardiovascular side effects including hypotension and syncope, the underlying mechanisms of which are largely unknown. We proposed that DOPA is a neurotransmitter in the central nervous system, but specific receptors for DOPA had not been identified. Recently, the gene product of ocular albinism 1 (OA1) was shown to possess DOPA-binding activity. It was unknown, however, whether or not OA1 is responsible for the actions of DOPA itself. Immunohistochemical examination revealed that OA1 was expressed in the nucleus tractus solitarii (NTS). OA1-positive cells adjacent to tyrosine hydroxylase-positive cell bodies and nerve fibers were detected in the depressor sites of the NTS. OA1 knockdown using oa1-specific shRNA-adenovirus vectors in the NTS reduced the expression levels of OA1 in the NTS. The prior injection of the shRNA against OA1 suppressed the depressor and bradycardic responses to DOPA but not to glutamate in the NTS of anesthetized rats. Thus OA-1 is a functional receptor of DOPA in the NTS, which warrants reexamination of the mechanisms for the therapeutic and untoward actions of DOPA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Baroreflex
  • Dihydroxyphenylalanine / adverse effects*
  • Dihydroxyphenylalanine / metabolism
  • Dihydroxyphenylalanine / pharmacology*
  • Dihydroxyphenylalanine / therapeutic use
  • Eye Proteins / metabolism*
  • Eye Proteins / physiology*
  • Humans
  • Hypotension / chemically induced*
  • Membrane Glycoproteins / metabolism*
  • Membrane Glycoproteins / physiology*
  • Neurotransmitter Agents
  • Parkinson Disease / drug therapy
  • Protein Binding
  • Rats
  • Receptors, Drug / metabolism*
  • Receptors, G-Protein-Coupled / metabolism*
  • Solitary Nucleus / metabolism
  • Syncope / chemically induced*

Substances

  • Eye Proteins
  • GPR143 protein, human
  • Membrane Glycoproteins
  • Neurotransmitter Agents
  • Receptors, Drug
  • Receptors, G-Protein-Coupled
  • Dihydroxyphenylalanine