Selective labeling of alpha-adrenergic receptors in caudate nucleus by [3H] dihydroergocryptine in the presence of spiperone-blocked dopamine receptors

Proc Natl Acad Sci U S A. 1978 May;75(5):2249-53. doi: 10.1073/pnas.75.5.2249.

Abstract

Because it was known that [(3)H]dihydroergocryptine can label alpha-adrenergic receptors as well as dopamine receptors, this study was done to establish the conditions under which [(3)H]dihydroergocryptine would be a reliable ligand for selective labeling of alpha-adrenergic receptors. The calf caudate was chosen because it contains both dopamine and adrenergic receptors, and 5 nM spiperone (spiroperidol) was used to block the neuroleptic/dopamine receptors. Thus, in the presence of spiperone, [(3)H]dihydroergocryptine exhibited saturable binding with a K(d) of 0.73 nM and a total number of sites of 150 fmol/mg of protein. The catechol neurotransmitters competed for [(3)H]dihydroergocryptine binding in the potencies order epinephrine > (-)-norepinephrine > dopamine, indicating that [(3)H]dihydroergocryptine (in the presence of 5 nM spiperone) was revealing alpha receptors. The alpha-adrenergic antagonists also competed for binding in the appropriate order: phentolamine > phenoxybenzamine > dibenamine. Finally, chlorpromazine was more potent than haloperidol in competing for [(3)H]dihydroergocryptine, also in accord with the properties of alpha receptors. These results with [(3)H]dihydroergocryptine as an alpha-adrenergic receptor ligand correlate well with those published by others for [(3)H]WB-4101.

MeSH terms

  • Adrenergic alpha-Antagonists / metabolism
  • Animals
  • Binding, Competitive
  • Cattle
  • Caudate Nucleus / metabolism*
  • Dihydroergotoxine / metabolism*
  • Neurotransmitter Agents / metabolism
  • Radioligand Assay
  • Receptors, Adrenergic / metabolism*
  • Receptors, Adrenergic, alpha / metabolism*
  • Receptors, Dopamine / metabolism
  • Spiperone / metabolism
  • Tranquilizing Agents / metabolism

Substances

  • Adrenergic alpha-Antagonists
  • Neurotransmitter Agents
  • Receptors, Adrenergic
  • Receptors, Adrenergic, alpha
  • Receptors, Dopamine
  • Tranquilizing Agents
  • Dihydroergotoxine
  • Spiperone