Neuropeptides blood-brain barrier

Several neuropeptides have been shown to play a role in anxiety but so far none has been developed as a drug largely because of their poor pharmacokinetic properties and difficulty in penetrating the blood-brain barrier. This situation may change in the future when drugs are developed that, though they may not be peptides, have a high affinity for the peptide receptors. 

The nervous system consists of various cell types that are functionally interconnected so as to allow efficient signal transmission throughout the system (see Chapter 48). The cells of the central nervous system are protected from potentially toxic compounds by the blood-brain barrier, which restricts entry of compounds into the nervous system (ammonia, however, is a notable exception). The brain cells communicate with each other and with other organs, through the synthesis of neurotransmitters and neuropeptides. Many of the neurotransmitters are derived from amino acids, most of which are synthesized within the nerve cell. Because the pathways of amino acid and neurotransmitter biosynthesis require cofactors (such as pyridoxal phosphate, thiamine pyrophosphate, and vitamin BI2), deficiencies of these cofactors can lead to neuropathies (dysfunction of specific neurons within the nervous system). 

Aminopeptidase N (EC 3.4.11) was shown to occur selectively in pericytes of brain capillaries (Krause et al. 1992). Fxmctionally this enzyme is involved in the degradation of polypeptides including bioactive peptides (Kenney and Turner 1987), such as those with vasoactive properties. The enzyme may therefore be a component of the blood-brain barrier modifying neuropeptides which themselves alter vascular permeability. In experimental allergic encephalomyelitis there is a down-regulation of pericyte aminopeptidase N accompanying the well-known transient and focal perturbation of the blood-brain barrier (Kunz etal. 1995). 

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