title: Identification of the alpha1L-adrenoceptor in rat cerebral cortex and possible relationship between alpha1L- and alpha1A-adrenoceptors.
abstract: OBJECTIVE
  In addition to alpha1A, alpha1B and alpha1D-adrenoceptors (ARs), putative alpha1L-ARs with a low affinity for prazosin have been proposed. The purpose of the present study was to identify the alpha1A-AR and clarify its pharmacological profile using a radioligand binding assay.
  
  
  METHODS
  Binding experiments with [3H]-silodosin and [3H]-prazosin were performed in intact tissue segments and crude membrane preparations of rat cerebral cortex. Intact tissue binding assays were also conducted in rat tail artery.
  
  
  RESULTS
  [3H]-silodosin at subnanomolar concentrations specifically bound to intact tissue segments and membrane preparations of rat cerebral cortex at the same density (approximately 150 fmol mg(-1) total tissue protein). The binding sites in intact segments consisted of alpha1A and alpha1L-ARs that had different affinities for prazosin, while the binding sites in membranes showed an alpha1A-AR-like profile having single high affinity for prazosin. [3H]-prazosin also bound at subnanomolar concentrations to alpha1A and alpha1B-ARs but not alpha1L-ARs in cerebral cortex; the binding densities being approximately 200 and 290 fmol mg(-1) protein in the segments and the membranes, respectively. In the segments of tail artery, [3H]-silodosin only recognized alpha1A-ARs, whereas [3H]-prazosin bound to alpha1A and alpha1B-ARs.
  
  
  CONCLUSIONS
  The present study clearly reveals the presence of alpha1L-ARs as a pharmacologically distinct entity from alpha1A and alpha1B-ARs in intact tissue segments of rat cerebral cortex but not tail artery. However, the alpha1L-ARs disappeared after tissue homogenization, suggesting their decomposition and/or their pharmacological profile changes to that of alpha1A-ARs.
authors.affiliation: Division of Pharmacology, Department of Biochemistry and Bioinformative Sciences, School of Medicine, University of Fukui, Eiheiji, Fukui, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Morishima
authors.forename: F
authors.initials: F
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Yoshiki
authors.forename: A S
authors.initials: AS
authors.lastname: Md Anisuzzaman
authors.forename: Z S
authors.initials: ZS
authors.lastname: Sathi
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: I
authors.initials: I
authors.lastname: Muramatsu
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000378:metabolism; D001665:Binding Sites; D002540:Cerebral Cortex / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013623:Tail / Q000098:blood supply
chemical_list: C547715:Adra1a protein, rat; C547718:Adra1b protein, rat; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D007211:Indoles; D018340:Receptors, Adrenergic, alpha-1; C095285:silodosin; D011224:Prazosin