CHARACTERIZATION OF I-2 IMIDAZOLINE AND A BINDING-SITES IN THE RAT AND HUMAN STOMACH

Radioligand binding experiments were carried out to identify and chara cterize nonadrenoceptor [H-3]idazoxan binding sites and [H-3](1,2-di-( 2-tolyl)guanidine) binding sites in the rat and human stomach. Further more, we examined two selected aspects of their potential functional s ignificance. Binding of [H-3]idazoxan (K-d = 11.1 nM and 12.4 mM, resp ectively) and [H-3]DTG (K-d = 932 nM and 242 nM, respectively) to cell membranes from rat and human stomach was rapid, reversible, specific and saturable. In rat stomach, binding of the radioligands was inhibit ed by imidazolines and by nonimidazoline sigma-site ligands, respectiv ely, at different rank orders of affinity, which suggests the existenc e of I-2-imidazoline binding sites as well as sigma(2)-sites. In two f unctional models, the direct effects of I-2-site ligands and sigma(2)- site ligands on gastric smooth muscle and glands were investigated. (1 ) Cirazoline, clonidine and 4-chloro-2-(2-imidazolin-2-ylamino)-isoind oline (BDF 6143) failed to contract the longitudinal muscle of the rat stomach fundus; BDF 6143 also failed to induce relaxation of this pre paration when it was precontracted with 30 mM KCl. (2) Clonidine, idaz oxan, BDF 6143, 1,2-di-(2-tolyl)guanidine, agmatine and (R)-3-(3-hydro xyphenyl)-N-propylpiperidine up to 100 mu M did not induce acid secret ion from rabbit isolated gastric glands. Our data provide evidence tha t the rat stomach is endowed with sigma(2) sites and I-2 binding sites in addition to the previously identified non-I-1/non-I-2 [H-3]clonidi ne binding sites. Our experiments also offer basic evidence of the exi stence of I-2 and a binding sites in the human stomach. Neither the I- 2 and [H-3]clonidine binding sites nor the a sites in rat stomach are directly related to a postsynaptic effect on gastric smooth muscle or to acid release from isolated gastric glands.