Characterization of non-adrenergic [3H]clonidine binding sites in rat stomach: high affinity of imidazolines, guanidines and sigma ligands

Naunyn Schmiedebergs Arch Pharmacol. 1995 May;351(5):561-4. doi: 10.1007/BF00171049.


We have identified and characterized non-adrenergic [3H]clonidine binding sites in rat stomach. The binding of [3H]clonidine was rapid, reversible, partly specific (as defined by cirazoline 0.1 nmol/l), saturable and of high affinity. The specific binding of [3H]clonidine to rat stomach membranes was concentration-dependently inhibited by various imidazolines and guanidines including the sigma site ligand 1,2-di-(2-tolyl)guanidine (DTG), by the butyrophenone derivative (+)-3-PPP[(R)-3-(3-hydroxyphenyl)-N-propylpiperidine]; the latter two compounds are also known to exhibit affinity for sigma sites. In contrast, rauwolscine, histamine, ranitidine and the non-hydrolysable GTP-analogue Gpp(NH)p (5' guanylylimidodiphosphate) did not, or with negligible affinity, inhibit [3H]clonidine binding. In most cases, the competition curves were best fitted to a two-site model. The rank order of affinity for the high affinity site (in a few cases for a single detectable site) was as follows: cirazoline > idazoxan > or = DTG > (+)-3-PPP > chlonidine > guanabenz > haloperidol. This rank order is not compatible with the pharmacological properties of either I1- or I2-imidazoline binding sites. However, the ability of haloperidol, (+)-3-PPP and DTG to displace [3H]clonidine (the latter two with high affinity) suggests that the [3H] clonidine binding sites in rat stomach may be related to sigma-like sites.

MeSH terms

  • Animals
  • Binding Sites
  • Clonidine / metabolism*
  • Dose-Response Relationship, Drug
  • Gastric Mucosa / metabolism*
  • Guanidines / metabolism*
  • Imidazoles / metabolism*
  • Kinetics
  • Rats
  • Rats, Wistar
  • Receptors, sigma / metabolism


  • Guanidines
  • Imidazoles
  • Receptors, sigma
  • Clonidine