Low permeability of the blood-brain barrier to nanomolar concentrations of immunoreactive alpha-melanotropin.
The permeability of the blood-brain barrier (BBB) to immunoreactive alpha-melanotropin (alpha-MSH) was quantified in rats pretreated with monosodium L-glutamic acid to deplete their CNS stores of endogenous alpha-MSH. The methodology, suitable for poorly permeable substances, monitored blood and brain tissue concentrations of alpha-MSH over 15 min following intravenous injection of 30 nmol synthetic alpha-MSH. Rate constants for entry of alpha-MSH into brain tissue were estimated from separate non-linear least-squares fits of connecting two- and one-compartment open models to plasma and extravascular brain tissue concentration data, respectively. Comparisons were made to rate constants measured similarly for 14C-inulin. The BBB had a low permeability to immunoreactive alpha-MSH, consistent with peptide penetrating the barrier by passive diffusion dependent upon the lipid solubility of the molecule.
Wilson
J F
JF
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff, UK.
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001812:Blood-Brain Barrier; D001923:Brain Chemistry / Q000187:drug effects; D005260:Female; D007457:Iodine Radioisotopes; D008297:Male; D008954:Models, Biological; D010539:Permeability; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012970:Sodium Glutamate / Q000494:pharmacology; D000521:alpha-MSH / Q000378:metabolism* / Q000493:pharmacokinetics
D001798:Blood Proteins; D007457:Iodine Radioisotopes; D000521:alpha-MSH; D012970:Sodium Glutamate