title: Antagonist characterization of atypical beta adrenoceptors in guinea pig ileum: blockade by alprenolol and dihydroalprenolol.
abstract: The present study was undertaken to further characterize the atypical beta adrenoceptor in guinea pig ileum. Tension was developed in isolated segments of ileum using transmural electrical stimulation of enteric cholingeric nerves. The ability of isoproterenol to relax the ileum, via beta-1 adrenoceptor and atypical beta adrenoceptor agonism, was measured. Propranolol (5 x 10(-6) M) and bromoacetylaprenololmetane blocked beta-1 adrenoceptors but, at the concentrations tested, were without affinity at atypical beta adrenoceptors. (-)-Alprenolol and (-)-dihydroalprenolol, however, acted as competitive antagonists at both sites (pA2 values of 8.2 and 8.81 at beta-1 adrenoceptors and 6.47 and 6.43 at atypical beta adrenoceptors, respectively). (-)-Alprenolol also exerted agonistic activity at the atypical beta adrenoceptor. [3H](-)-Dihydroproalprenolol failed to identify beta-1 adrenoceptors or atypical beta adrenoceptors but, instead, bound to a putative lipophilic site unrelated to ileal adrenoceptors. Before this study, nadolol (pA2 = 4.7) was the only documented antagonist at the atypical beta adrenoceptor in guinea pig ileum. Thus, the present results detail two additional pharmacological probes which exhibit about a 100-fold greater affinity than nadolol for the atypical site.
authors.affiliation: Department of Pharmacology, University of Houston, TX.
authors.forename: D R
authors.initials: DR
authors.lastname: Blue
authors.forename: R A
authors.initials: RA
authors.lastname: Bond
authors.forename: N
authors.initials: N
authors.lastname: Adham
authors.forename: R
authors.initials: R
authors.lastname: Delmendo
authors.forename: A D
authors.initials: AD
authors.lastname: Michel
authors.forename: R M
authors.initials: RM
authors.lastname: Eglen
authors.forename: R L
authors.initials: RL
authors.lastname: Whiting
authors.forename: D E
authors.initials: DE
authors.lastname: Clarke
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000526:Alprenolol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D004082:Dihydroalprenolol / Q000494:pharmacology*; D004347:Drug Interactions; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; C045331:bromoacetylalprenololmenthane; D000526:Alprenolol; D011433:Propranolol; D007545:Isoproterenol