title: Identification and characterization of a high-affinity peripheral-type benzodiazepine receptor in rabbit urinary bladder.
abstract: The present study used radioligand binding and in vitro contractility experiments to identify and characterize a peripheral-type benzodiazepine receptor PBR in rabbit urinary bladder. [3H]PK11195 bound to bladder membranes with high-affinity and density (Kd = 5.2 nM., Bmax = 268 fmol./mg. protein), indicating the presence of a PBR. [3H]flunitrazepam bound with high-affinity and density (Kd = 1.2 nM., Bmax = 48 fmol./mg. protein). The rank order potency of various benzodiazepines and isoquinoline carboxamides in displacing the binding of [3H]PK11195 was Ro5-4864 > diazepam = flunitrazepam >> Ro15-1788 = clonazepam. Ro5-4864 and PK11195 inhibited nerve-evoked contractions in a concentration-dependent manner (IC50 = 42 microM. and 56 microM., respectively). Carbachol- and KCl-induced contractions were also inhibited by Ro5-4864 and PK11195. KCl-induced contractions were inhibited to a greater extent than carbachol-induced or field-stimulated contractions with all the drugs tested. Both Ro5-4864 and PK11195 significantly increased the ED50 for calcium-induced contractions following a cholinergic stimulus compared with control. These data demonstrate the presence of a PBR in urinary bladder capable of altering contractility in vitro through modulation of calcium activity.
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
authors.forename: R J
authors.initials: RJ
authors.lastname: Smyth
authors.forename: E J
authors.initials: EJ
authors.lastname: Uhlman
authors.forename: M R
authors.initials: MR
authors.lastname: Ruggieri
mesh_terms: D000818:Animals; D005442:Flumazenil / Q000494:pharmacology; D005445:Flunitrazepam / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000737:chemistry* / Q000187:drug effects; D011817:Rabbits; D011963:Receptors, GABA-A / Q000302:isolation & purification*; D001743:Urinary Bladder / Q000737:chemistry* / Q000187:drug effects
chemical_list: D058787:GABA-A Receptor Antagonists; D007546:Isoquinolines; D011963:Receptors, GABA-A; D005442:Flumazenil; D005445:Flunitrazepam; C037850:PK 11195