Blood-brain barrier , peptides crossing

D) Because they cannot cross the blood-brain barrier, peptides are not found in the brain... 

D. J., Douglas C. L, Boules M., Stewart J.A., Zhao L., Lacy B., Cusack B., Fauq A., Richelson E. Peptide nucleic acids targeted to the neurotensin receptor and administered i.p. cross the blood-brain barrier and specifically reduce gene expression. Proc. Natl Acad. Sci. USA 1999 96 7053-7058. 

The peptides will now be considered individually in some detail. It must be noted that the large molecular size of the peptides means that they are even less likely to cross the blood-brain barrier than classical transmitters and the instability of peptides means that full functional studies require non-peptide agonists and antagonists. Whereas nature has provided morphine and medicinal chemists have made naloxone, tools are lacking for many other peptides. 

Peptides do not readily cross the blood-brain barrier to enter the brain. 

When injected intravenously, kinins produce a rapid fall in blood pressure that is due to their arteriolar vasodilator action. The hypotensive response to bradykinin is of very brief duration. Intravenous infusions of the peptide fail to produce a sustained decrease in blood pressure prolonged hypotension can only be produced by progressively increasing the rate of infusion. The rapid reversibility of the hypotensive response to kinins is due primarily to reflex increases in heart rate, myocardial contractility, and cardiac output. In some species, bradykinin produces a biphasic change in blood pressure—an initial hypotensive response followed by an increase above the preinjection level. The increase in blood pressure may be due to a reflex activation of the sympathetic nervous system, but under some conditions, bradykinin can directly release catecholamines from the adrenal medulla and stimulate sympathetic ganglia. Bradykinin also increases blood pressure when injected into the central nervous system, but the physiologic significance of this effect is not clear, since it is unlikely that kinins cross the blood-brain barrier. 

D-Ala-deltorphin-I and -II transverse the blood brain barrier in vivo and in vitro [51]. Recently, D-Ala-deltorphin-II was identified as a transport substrate of organic anion transporting polypeptides (Oatp/OATP), a family of polyspecific membrane transporters, strongly expressed at the rat and human blood brain barrier [52]. Modified analogues of these peptides were synthesized to improve their transit across the blood brain barrier [48,49,53]. Because they resist enzyme degradation and can cross endothelial barriers into the CNS, the deltorphins meet the criteria for peptides with potential for systemic administration. 

Costantino, L., et al. (2005), Peptide-derivatized biodegradable nanoparticles able to cross the blood-brain barrier, J. Controlled Release, 108(1), 84-96. 

Deltanyne dronabinol, delta sleep-inducing peptide (DSIP) is a nonapeptide, originally isolated from the extracorporeal dialysate of cerebral venous blood of rabbits, and subsequently was synthesized. It induces sleep when administered intravenously in animal models. It can cross the blood-brain-barrier and has ANTICONVULSANT and HYPNOTIC actions it also inhibits pituitary ACTH secretion. Deltasone prednisone. 

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