title: Functional and radioligand binding characterization of the α1L-adrenoceptor subtype of the human vas deferens.
abstract: Alpha1 -adrenoceptor antagonists can cause ejaculatory dysfunction as an adverse effect. Contractions of the human vas deferens are mediated via α1A -adrenoceptors, and this study investigated whether the low affinity state of this receptor (α1L -adrenoceptor) is involved in mediating contractions of this tissue. The potency of agonists and the affinity of receptor subtype selective antagonists were determined in functional experiments and in [(3) H]tamsulosin binding experiments to identify the α1 -adrenoceptor subtype population present in the human vas deferens. The α1A -adrenoceptor selective agonist A61603 was a full agonist and was 250-fold more potent than noradrenaline. Prazosin antagonized contractile responses to phenylephrine with a low affinity (pKd = 8.6). Only high concentrations of RS17053 antagonized responses to phenylephrine and yielded a relatively low affinity estimate of 7.0. BMY7378 (α1D -adrenoceptor selective) gave a low affinity estimate (pKd = 6.7), whilst tamsulosin (α1A - and α1D -adrenoceptor selective) had a high affinity (pKd = 9.9). [(3) H]Tamsulosin bound to human vas deferens membranes with a high affinity (pKd = 10.0). Prazosin, RS17053 and BMY7378 competed with [(3) H]tamsulosin with low affinities for a single population of binding sites (pKd values of 8.5, 7.2 and 6.3, respectively). These functional and radioligand binding data indicate that the human vas deferens possesses a homogeneous population of α1 -adrenoceptors which have the pharmacological properties of the putative α1L -adrenoceptor, the same functional receptor previously identified in the human prostate.
authors: Department of Urology, Royal Hallamshire Hospital, Sheffield, S10 2JF, UK.
authors: B J
authors: BJ
authors: Davis
authors: M
authors: M
authors: Wiener
authors: C R
authors: CR
authors: Chapple
authors: D J
authors: DJ
authors: Sellers
authors: R
authors: R
authors: Chess-Williams
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology*; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011869:Radioligand Assay; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013449:Sulfonamides / Q000378:metabolism / Q000494:pharmacology; D000077409:Tamsulosin; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014316:Tritium / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism*
chemical_list: C094643:A 61603; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D007093:Imidazoles; D007211:Indoles; D010879:Piperazines; C099495:RS 17053; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; D013764:Tetrahydronaphthalenes; D014316:Tritium; D010656:Phenylephrine; D000077409:Tamsulosin; C053428:BMY 7378; D011224:Prazosin
keywords: A61603; RS17053; [3H]tamsulosin; alpha1-adrenoceptor; human vas deferens