Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the "dopamine receptor"

Proc Natl Acad Sci U S A. 1972 Aug;69(8):2145-9. doi: 10.1073/pnas.69.8.2145.

Abstract

An adenylate cyclase that is activated specifically by low concentrations of dopamine has been demonstrated in homogenates of caudate nucleus of rat brain. A half-maximal increase in the activity of the enzyme occurred in the presence of 4 muM dopamine. Concentrations of dopamine as low as 0.3 muM stimulated the activity of the enzyme. The adenylate cyclase activity of the homogenates was also stimulated by low concentrations of apomorphine, a substance known to mimic the physiological and pharmacological effects of dopamine. The stimulatory effect of dopamine was blocked by low concentrations of either haloperidol or chlorpromazine, agents known to block the actions of dopamine in mammalian brain. The results suggest that dopamine-sensitive adenylate cyclase may be the receptor for dopamine in mammalian brain. The isolation of this enzyme from caudate nucleus should facilitate the search for new therapeutic agents useful in the treatment of extrapyramidal diseases.

MeSH terms

  • Adenylyl Cyclases / isolation & purification*
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Apomorphine / pharmacology
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / enzymology*
  • Chlorpromazine / pharmacology
  • Cyclic AMP / analysis
  • Dopamine / pharmacology*
  • Dopamine Antagonists
  • Enzyme Activation / drug effects
  • Haloperidol / pharmacology
  • Isoproterenol / pharmacology
  • Male
  • Methods
  • Norepinephrine / pharmacology
  • Phentolamine / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Drug

Substances

  • Adrenergic alpha-Antagonists
  • Dopamine Antagonists
  • Receptors, Drug
  • Cyclic AMP
  • Adenylyl Cyclases
  • Haloperidol
  • Isoproterenol
  • Apomorphine
  • Chlorpromazine
  • Dopamine
  • Norepinephrine
  • Phentolamine