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 (-MSH) was quantified in rats pretreated with monosodium l-glutamic acid to deplete their CNS stores of endogenous -MSH. The methodology, suitable for poorly permeable substances, monitored blood and brain tissue concentrations of -MSH over 15 min following intravenous injection of 30 nmol synthetic -MSH. Rate constants for entry of -MSH into brain tissue were estimated from separate nonlinear 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 -MSH, consistent with peptide penetrating the barrier by passive diffusion dependent upon the lipid solubility of the molecule.