Skip to main content
Log in

Low permeability of the blood-brain barrier to nanomolar concentrations of immunoreactive alpha-melanotropin

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

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

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Banks WA, Kastin AJ (1985a) Permeability of the blood-brain barrier to neuropeptides: the case for penetration. Psychoneuroendocrinology 10:385–399

    Google Scholar 

  • Banks WA, Kastin AJ (1985b) Peptides and the blood-brain barrier: lipophilicity as a predictor of permeability. Brain Res Bull 15:287–292

    Google Scholar 

  • Beckwith BE, Sandman CA (1978) Behavioral influences of the neuropeptides ACTH and MSH: a methodological review. Neurosci Biobehav Rev 2:311–338

    Google Scholar 

  • Cornbleet PJ, Gochman N (1979) Incorrect least-squares regression coefficients in method comparisons analysis. Clin Chem 25:432–438

    Google Scholar 

  • Cornford EM, Braun LD, Crane PD, Oldendorf WH (1978) Blood-brain barrier restriction of peptides and the low uptake of enkephalins. Endocrinology 103:1297–1303

    Google Scholar 

  • De Rotte AA, Bouman HJ, van Wimersma Greidanus TjB (1980) Relationships between α-MSH levels in blood and in cerebrospinal fluid. Brain Res Bull 5:375–381

    Google Scholar 

  • De Wied D (1978) Behavioural effects of neuropeptides related to β-LPH. In: Hughes J (ed) Centrally acting peptides. Macmillan Press, London, pp 241–251

    Google Scholar 

  • Dupont A, Kastin AJ, Labrie F, Pelletier G, Puviani R, Schally AV (1975) Distribution of radioactivity in organs of the rat and mouse after injection of [125I] α-melanocyte-stimulating hormone. J Endocrinol 64:237–241

    Google Scholar 

  • Eskay RL, Brownstein MJ, Long RT (1979) α-Melanocyte-stimulating hormone: reduction in adult rat brain after monosodium glutamate treatment of neonates. Science 205:827–829

    Google Scholar 

  • Fenstermacher JD, Blasberg RG, Patlak CS (1981) Methods for quantifying the transport of drugs across brain barrier systems. Pharmacol Ther 14:217–248

    Google Scholar 

  • Greenberg R, Whalley CE, Jourdikian F, Mendelson IS, Walter R, Nikolics K, Coy DH, Schally AV, Kastin AJ (1976) Peptides readily penetrate the blood-brain barrier: uptake of peptides by synaptosomes is passive. Pharmacol Biochem Behav [Suppl 1] 5:151–158

    Google Scholar 

  • Kastin AJ, Nissen C, Nikolics K, Medzihradszky K, Coy DH, Teplan I, Schally AV (1976) Distribution of 3H-α-MSH in rat brain. Brain Res Bull 1:19–26

    Google Scholar 

  • Kastin AJ, Olson RD, Schally AV, Coy DH (1979) CNS effects of peripherally administered brain peptides. Life Sci 25:401–414

    Google Scholar 

  • La Du BN, Mandel HG, Way EL (1971) Fundamentals of drug metabolism and drug disposition. Williams & Wilkins, Baltimore

    Google Scholar 

  • McIntosh JEA, McIntosh RP (1980) Mathematical modelling and computers in endocrinology. Springer Verlag, Berlin Heidelberg New York

    Google Scholar 

  • Meisenberg G, Simmons WH (1983) Peptides and the blood-brain barrier. Life Sci 32:2611–2623

    Google Scholar 

  • O'Donohue TL, Dorsa DM (1982) The opiomelanotropinergic neuronal and endocrine systems. Peptides 3:353–395

    Google Scholar 

  • Ohno K, Pettigrew KD, Rapoport SI (1978) Lower limits of cerebrovascular permeability to nonelectrolytes in the conscious rat. Am J Physiol 235:H299-H307

    CAS  PubMed  Google Scholar 

  • Oldendorf WH (1975) Permeability of the blood-brain barrier. In: The basic neurosciences. The nervous system, vol 1. Tower DB (ed) Raven Press, New York, pp 279–289

    Google Scholar 

  • Olney JW (1969) Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 164:719–721

    Google Scholar 

  • Pardridge WM, Mietus LJ (1981) Enkephalin and blood-brain barrier: studies of binding and degradation in isolated brain microvessels. Endocrinology 109:1138–1143

    Google Scholar 

  • Pelletier G, Labrie F, Kastin AJ, Schally AV (1975) Radioautographic localization of radioactivity in rat brain after intracarotid injection of 125I-α-melanocyte-stimulating hormone. Pharmacol Biochem Behav 3:671–674

    Google Scholar 

  • Rapoport SI, Klee WA, Pettigrew KD, Ohno K (1980) Entry of opioid peptides into the central nervous system. Science 207:84–86

    Google Scholar 

  • Sharma RR, Vimal RLP (1984) Theoretical interpretation of extraction (in brain) of peptides including concentration variations. Brain Res 308:201–214

    Google Scholar 

  • Wilson JF, Morgan MA (1979a) A radioimmunoassay for alpha-melanotropin in rat plasma. J Pharmacol Methods 2:97–116

    Google Scholar 

  • Wilson JF, Morgan MA (1979b) α-Melanotropin-like substances in the pituitary and plasma of Xenopus laevis in relation to colour change response. Gen Comp Endocrinol 38:172–182

    Google Scholar 

  • Wilson JF, Anderson S, Snook G, Llewellyn KD (1984) Quantification of the permeability of the blood-CSF barrier to α-MSH in the rat. Peptides 5:681–685

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wilson, J.F. Low permeability of the blood-brain barrier to nanomolar concentrations of immunoreactive alpha-melanotropin. Psychopharmacology 96, 262–266 (1988). https://doi.org/10.1007/BF00177572

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00177572

Key words

Navigation