Investigation of alpha 1-adrenoceptor subtypes in canine aorta, using alkylating agents

Can J Physiol Pharmacol. 1994 Jan;72(1):97-103. doi: 10.1139/y94-015.

Abstract

The ability of putative selective irreversible ligands SZL-49 (1-(4-amino-6,7-dimethoxy-2,5-diene-2-carbonyl)) and CEC (chlorethylclonidine), for alpha 1A and alpha 1B adrenoceptor subtypes, respectively, to affect alpha 1-adrenoceptors of canine aorta microsomal membranes was investigated. These membranes contain an apparently homogeneous population of [3H]prazosin binding sites. SZL-49, like phenoxybenzamine, abolished all binding of [3H]prazosin. CEC abolished 75% of the prazosin binding sites under the most stringent conditions we applied. However, the remaining 25% of binding sites was identical in affinity for prazosin with control membranes, and competition studies of other subtype-selective ligands revealed unchanged ability to complete against CEC-sensitive and -insensitive sites. We concluded that SZL-49 and CEC are not alpha 1A- and alpha 1B-adrenoceptor selective under in vitro conditions. Our data led to the hypothesis that canine aortic membranes contain exclusively alpha 1B-adrenoceptors but that current tools for identifying alpha 1-adrenoceptor subtypes proved inadequate in vitro in this study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-Agonists / pharmacokinetics
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacokinetics
  • Adrenergic alpha-Antagonists / pharmacology
  • Alkylating Agents / pharmacology*
  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Binding, Competitive / drug effects
  • Clonidine / analogs & derivatives
  • Clonidine / pharmacology
  • Dioxanes / pharmacology
  • Dogs
  • Female
  • In Vitro Techniques
  • Male
  • Mesenteric Veins / drug effects
  • Mesenteric Veins / metabolism
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Oxymetazoline / pharmacology
  • Prazosin / analogs & derivatives
  • Prazosin / pharmacokinetics
  • Prazosin / pharmacology
  • Radioligand Assay
  • Receptors, Adrenergic, alpha-1 / drug effects
  • Receptors, Adrenergic, alpha-1 / metabolism*

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Alkylating Agents
  • Dioxanes
  • Receptors, Adrenergic, alpha-1
  • SZL 49
  • chlorethylclonidine
  • Oxymetazoline
  • (2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane
  • Clonidine
  • Prazosin