Beta-adrenergic receptor subtypes mediating lipolysis in porcine adipocytes. Studies with BRL-37344, a putative beta3-adrenergic agonist

Comp Biochem Physiol C Toxicol Pharmacol. 2000 May;126(1):11-20. doi: 10.1016/s0742-8413(00)00086-4.

Abstract

The beta3-selective adrenergic receptor ligand BRL 37344 (BRL) was used to differentiate the presence and functional role of beta-adrenergic receptor (betaAR) subtypes in pig tissues. BRL did not stimulate adenylyl cyclase in membrane preparations or increase lipolysis from pig adipocytes. In contrast to some species, BRL appears to be a poor agonist for the pig betaAR and is not a useful betaAR ligand. Based on displacement of [3H]dihydroalprenolol binding, BRL exhibited a 100-fold selectivity for pig betaAR subtypes in adipose and skeletal muscle membranes. The high affinity site was proposed to be the beta2AR. When used as an antagonist, BRL blockade of the high affinity site did not interfere with isoproterenol-stimulated lipolysis but did inhibit adenylyl cyclase activation. Results indicate that the high affinity betaAR (betaAR) is not linked to lipolysis, possibly due to intracellular compartmentalization. Therefore, betaAR subtypes may have function-specific effects.

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Cell Fractionation
  • Dihydroalprenolol / metabolism
  • Ethanolamines / pharmacology*
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / metabolism
  • Isoproterenol / pharmacology
  • Lipolysis / drug effects
  • Lipolysis / physiology*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Receptors, Adrenergic, beta / classification
  • Receptors, Adrenergic, beta / physiology*
  • Swine

Substances

  • Adrenergic beta-Agonists
  • Ethanolamines
  • Receptors, Adrenergic, beta
  • BRL 37344
  • Dihydroalprenolol
  • Adenylyl Cyclases
  • Isoproterenol