Neuropeptide FF (
NPFF) and
neuropeptide AF (NPAF) are two mammalian amidated
neuropeptides which are highly concentrated in the posterior pituitary, spinal cord, hypothalamus and medulla. One precursor
protein has been identified in mouse, rat, bovine and human brain. The precursor contains a single copy of both
peptides, followed by a
glycine residues necessary for amidation and flanked by basic residues necessary for processing by
enzymes. In the brain,
NPFF-like immunoreactive neurons are found in the hypothalamus and medulla. These systems may be associated with observed effects of
NPFF on memory and autonomic regulation, respectively. A hypothalamo-pituitary pathway may be involved in neuroendocrine regulation. This is supported by lack of
NPFF in the pituitary gland of
vasopressin-deficient Brattleboro rats. It is also possible that
NPFF acts as a
hormone, as it has been detected in human plasma. The spinal cord contains an intrinsic
NPFF-ir neuron system, with cell bodies in the dorsal horn and around the central canal. Nerve terminals are highly concentrated in the superficial laminae of the dorsal horn, where
NPFF-immunoreactivity can be released by, e.g.,
potassium and
substance P. One specific high-affinity binding site, distinct from binding sites for other
peptides, has been characterized in the rat and human brain and spinal cord. The
NPFF receptor appears to be coupled to a
G-protein, but details of the second messenger systems have not been clarified yet. Intracerebroventricular injection of
NPFF induces a vigorous abstinence syndrome in
morphine-tolerant rats. Although clear antiopioid-like effects of
NPFF on
pain have been observed, some studies have also demonstrated long-lasting
analgesic effects. These findings and the observed increase in
NPFF-immunoreactivity in the cerebrospinal fluid during development of
opiate tolerance render
NPFF an interesting and challenging target of investigation.