title: Characterization of non-adrenergic [3H]clonidine binding sites in rat stomach: high affinity of imidazolines, guanidines and sigma ligands.
abstract: 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.
authors.affiliation: Institut für Pharmakologie und Toxikologie der Rheinischen Friedrich-Wilhelms-Universität Bonn, Germany.
authors.forename: G J
authors.initials: GJ
authors.lastname: Molderings
authors.forename: K
authors.initials: K
authors.lastname: Donecker
authors.forename: M
authors.initials: M
authors.lastname: Göthert
mesh_terms: D000818:Animals; D001665:Binding Sites; D003000:Clonidine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism*; D007093:Imidazoles / Q000378:metabolism*; D007700:Kinetics; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000378:metabolism
chemical_list: D006146:Guanidines; D007093:Imidazoles; D017480:Receptors, sigma; D003000:Clonidine