Furthermore, some peptides have been suggested to maintain a long extracellular half-life ( Ludwig and Leng, 2006), thereby maintaining activity during the temporal window required for diffusion. In many parts of the brain, the expression patterns of peptide-containing processes and the homologous peptide receptors
overlap, consistent with a local action of the neuropeptide. selleck inhibitor But in a large number of CNS loci, the anatomical expression of a particular peptide and its receptors may be in completely different regions of the brain, as noted in the extensive review of such anatomical mismatches by Herkenham (1987). This peptide-receptor mismatch could be simply a nonfunctional throwback to some partial preservation of selleckchem an interaction that was important in the evolutionary past but is no longer relevant. Alternately, for peptides such as oxytocin, there may be massive release due to the simultaneous activation of a majority of oxytocin neurons within the brain; this can raise the extracellular oxytocin in the area of the supraoptic nucleus to a level 100-fold greater than circulating oxytocin (Ludwig and Leng, 2006), allowing diffusion of a higher concentration of peptide to activate oxytocin
receptors at more distant sites than would be possible with asynchronous firing. Arguing against long distance release and response as a general rule is the fact that a number of neuropeptides, for instance, NPY, dynorphin, or somatostatin, are synthesized and released by many unrelated groups of neurons in different regions of the brain. Any specific role of the peptide relevant to the releasing neuron would be negated if the same peptide from other brain regions was diffusing long distances. Furthermore, peptidases actively break down peptides extracellularly,
reducing the effective distance an active peptide may diffuse. Depending on the size, all presence of disulfide bonds which increase peptide half-life, amidation, and chemical confirmation of the peptide, peptide half-lives can vary. Administration of a particular peptide or other modulator into a receptor-rich region of the brain lacking in that particular peptide can generate very selective functional responses, suggesting a functional plausibility to volume transmission. However, neuropeptide receptors simply respond to peptide, and even if the response is specific for a particular brain region or circuit, it may be simply a response of selective circuit activation or inhibition that may not normally occur.