Melanotropic peptides increase permeability of plasma/cerebrospinal fluid barrier
Rudman, D.; Kutner, M.H.
American Journal of Physiology 234(3): E327-E332
1978
ISSN/ISBN: 0002-9513 PMID: 204198 Document Number: 133963
A previous study showed intracisternal injection of melanotropic peptides caused a 3-5 times increase in concentration of protein in cerebrospinal fluid (CSF) within 15 min. This finding suggested that the peptides modify permeability of the plasma/CSF barrier. The present study examined the effect of 4 melanotropic peptides ACTH, .alpha.- and .beta.-melanocyte-stimulating hormones (MSH), and choroid plexus peptide IIF) (agonists) on permeability of the plasma/CSF barrier to a series of radioactive substances, which are transported across this barrier by diverse mechanisms: albumin, mannitol, sucrose, inulin, glucose, .alpha.-aminoisobutyric acid and valine (circulants). In anesthetized rabbits, 6-10 .mu.Ci of circulant was injected i.v. and 1-1000 .mu.g of agonist intracisternally. At 15 min intervals during the next 75 min, radioactivity in CSF and in plasma was measured. Intracisternal injection of 1000 .mu.g of the melanotropic peptides did not influence the rate of removal of any circulant from the plasma. In contrast, injection of the peptides increased the rate of appearance of albumin, mannitol, inulin and sucrose in the CSF 2-4 times over controls. The effect was proportional to dose. Minimal effective dose (MED) was generally 1 .mu.g for .alpha.-MSH and .beta.-MSH, 10 .mu.g for ACTH and 100 .mu.g for IIF. Trypsinized peptides were inactive. MED was 100 times higher by the i.v. route. The melanotropic peptides did not accelerate appearance of radioactivity in CSF after injection of labeled glucose, .alpha.-aminoisobutyric acid, or valine. Intracisternally injected arginine vasopressin (100 .mu.g), norepinephrine (100 .mu.g), histamine (100 .mu.g) and serotonin (100 .mu.g) had no effect on rate of entry of any circulant from plasma to CSF.