Evidence for a multi-site model of the rat brain sigma receptor

Eur J Pharmacol. 1989 Apr 25;163(2-3):309-18. doi: 10.1016/0014-2999(89)90200-8.


Irradiation of rat brain membranes with light of 254 nm, a treatment which modifies ultra-violet absorbing residues in proteins, decreased binding of both [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ([ 3H](+)-3-PPP) and [3H]1,3-di-o-tolylguanidine ([3H]DTG) to sigma receptors. For [3H](+)-3-PPP, this was due to a decreased Bmax. In contrast, irradiation markedly increased binding of [3H](+)-N-allylnormetazocine ([3H](+)-SKF 10,047) due to a decrease in the Kd. Both unlabeled DTG and haloperidol were competitive inhibitors of [3H](+)-3-PPP binding to untreated membranes, causing an increase in the Kd and no change in the Bmax. The benzomorphans, (+)-SKF 10,047 and (+)-pentazocine, were uncompetitive inhibitors, causing a decrease in both the Kd and Bmax for [3H](+)-3-PPP. Finally, the ability of DTG and (+)-3-PPP to inhibit binding of [3H](+)-SKF 10,047 was markedly reduced by ultra-violet irradiation, whereas irradiation had little effect on the potency of unlabeled (+)-SKF 10,047 and (+)-pentazocine. These data suggest that sigma-related (+)-benzomorphans and non-benzomorphans interact either with distinct, allosterically coupled sites on the same sigma receptor macromolecule or with different populations of sigma receptor types.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / radiation effects
  • In Vitro Techniques
  • Male
  • Membranes / metabolism
  • Membranes / radiation effects
  • Models, Biological
  • Phenazocine / analogs & derivatives
  • Phenazocine / metabolism
  • Piperidines / metabolism
  • Rats
  • Rats, Inbred Strains
  • Receptors, Opioid / metabolism*
  • Receptors, Opioid, delta
  • Synaptosomes / metabolism
  • Synaptosomes / radiation effects
  • Ultraviolet Rays


  • Piperidines
  • Receptors, Opioid
  • Receptors, Opioid, delta
  • SK&F 10047
  • preclamol
  • Phenazocine