title: Lung tissue binding of iodobenzyl-propanediamine: involvement of beta-adrenergic receptors.
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.
authors.affiliation: Istituto di Fisiologia Clinica del CNR, Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Paci
authors.forename: G
authors.initials: G
authors.lastname: Ciarimboli
authors.forename: M
authors.initials: M
authors.lastname: Miniati
authors.forename: F
authors.initials: F
authors.lastname: Cocci
authors.forename: F
authors.initials: F
authors.lastname: Piras
authors.forename: M
authors.initials: M
authors.lastname: Pistolesi
mesh_terms: D000818:Animals; D066298:In Vitro Techniques; D007462:Iodobenzenes / Q000378:metabolism*; D020120:Iodocyanopindolol; D008168:Lung / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
chemical_list: D007462:Iodobenzenes; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; C036739:N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine; D011433:Propranolol; D010869:Pindolol