Gj. Molderings et al., CHARACTERIZATION OF NONADRENERGIC [H-3] CLONIDINE BINDING-SITES IN RAT STOMACH - HIGH-AFFINITY OF IMIDAZOLINES, GUANIDINES AND SIGMA-LIGANDS, Naunyn-Schmiedeberg's archives of pharmacology, 351(5), 1995, pp. 561-564
We have identified and characterized non-adrenergic [H-3]clonidine bin
ding sites in rat stomach. The binding of [H-3]clonidine was rapid, re
versible, partly specific (as defined by cirazoline 0.1 mmol/l; 68% sp
ecific binding at [H-3]clonidine 10 nmol/l), saturable and of high aff
inity. The specific binding of [H-3]clonidine to rat stomach membranes
was concentration-dependently inhibited by various imidazolines and g
uanidines including the sigma site ligand 1,2-di-(2-tolyl)guanidine (D
TG), by the butyrophenone derivative haloperidol and by the piperidine
derivative 3-PPP[(R)-3-(3-hydroxyphenyl)-N-propylpiperidine]; the lat
ter two compounds are also known to exhibit affinity for sigma sites.
In contrast, rauwolscine, histamine, ranitidine and the non-hydrolysab
le GTP-analogue Gpp(NH)p (5' guanylylimidodiphosphate) did not, or wit
h negligible affinity, inhibit [H-3]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 sin
gle detectable site) was as follows: cirazoline>idazoxan greater than
or equal to DTG> (+)-3-PPP> clonidine>guanabenz>haloperidol. This rank
order is not compatible with the pharmacological properties of either
I-1- or I-2-imidazoline binding sites. However, the ability of halope
ridol, (+)-3-PPP and DTG to displace [H-3]clonidine (the latter two wi
th high affinity) suggests that the [H-3] clonidine binding sites in r
at stomach may be related to sigma-like sites.