Characterization of prostaglandin E receptors in canine small intestine using [3H] prostaglandin E1 binding

Abstract Prostaglandin E (PGE) receptors in canine small intestinal mucosal and muscle membrane preparations were labeled with [ 3 H] PGE 1 . Saturable, high affinity binding of [ 3 H] PGE 1 was observed in both preparations. The density of binding sites (fmol/mg protein) was 39 for mucosal membranes and 60 for muscle membranes, with corresponding dissociation constants of 10.6 nM and 5.8 nM, respectively. [ 3 H] PGE 1 binding sites in both preparations showed stereospecificity and high affinity for natural PGE 1 and PGE 2 , but not for I or F-type PGs. Synthetic PGEs such as misoprostol and enisoprost had lower affinity than PGE 1 or PGE 2 . Several analogs of enisoprost bound weakly to the binding sites. A highly significant correlation (C.C. = 0.9) was demonstrated between mucosal and muscle binding potency for a series of enisoprost analogs. There was also a significant positive correlation between the receptor binding potency and rat diarrheagenic activity for these analogs. These results indicate that PGE receptors in canine intestinal mucosa and muscle can be directly studied with [ 3 H] PGE 1 binding. The mucosal and muscle PGE receptors may have similar ligand binding specificity. We speculate that these receptors are likely to be associated with the diarrheagenic activity of PGEs.