Lung tissue binding of iodobenzyl-propanediamine: involvement of beta-adrenergic receptors

J Pharm Biomed Anal. 1989;7(12):1467-72. doi: 10.1016/0731-7085(89)80152-9.

Abstract

The basic compound N-N-N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3- propanediamine (HIPDM) accumulates in human and rabbit lungs, where it forms a slowly effluxable pool. In isolated perfused rat lung, HIPDM is taken up by a saturable, energy-independent mechanism, which is competitively inhibited by imipramine, chlorpromazine and propranolol. To ascertain whether beta-adrenergic receptors are involved in the binding process of HIPDM to lung tissue, the ability of unlabelled HIPDM to displace the beta-adrenergic receptor ligand [125I]iodocyanopindolol (ICYP) from rabbit lung beta-receptors was examined. Lung microsomal membrane fractions (75 micrograms ml-1) were incubated at 37 degrees C for 3 h with 68 pM ICYP (with or without 1 microM of (+/-)-propranolol) in the presence of HIPDM (10(-10)-10(-3) M). Bound and free radioactivity were separated through glass-fibre filters and the retained radioactivity was counted in a gamma-spectrometer. HIPDM competed with ICYP for beta-adrenoceptors (13% displacement at 10(-5) M. 50% at 5 x 10(-5) M, and 90% at 2 x 10(-4) M). The inhibition curve of ICYP binding by HIPDM was similar to that observed for (-)-noradrenaline. Although the results of the in vitro studies cannot be extrapolated to in vivo conditions, they suggest that beta-adrenergic receptors may be involved in the observed lung uptake of the basic amine HIPDM.

MeSH terms

  • Animals
  • In Vitro Techniques
  • Iodobenzenes / metabolism*
  • Iodocyanopindolol
  • Lung / metabolism*
  • Microsomes / metabolism
  • Pindolol / analogs & derivatives
  • Pindolol / metabolism
  • Propranolol / pharmacology
  • Rabbits
  • Receptors, Adrenergic, beta / metabolism*

Substances

  • Iodobenzenes
  • Receptors, Adrenergic, beta
  • Iodocyanopindolol
  • N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine
  • Propranolol
  • Pindolol