section 31.1
Hypothalamus
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2 9
F I G U R E 3 1 -2
Dipeptide signals in the posttranslational processing o f horm ones. This figure presents schem atic structures o f three
precursor m olecules that contain one or m ore o f three sequences characteristic o f H m et-enkephalin, S leu-enkephalin,
E33 m elanocyte-stim ulating horm one. Bioactive peptides (like ACTH, endorphins, enkephalins, and dynorphins) are
released by proteolytic enzym es during processing o f the precursor m olecules. Cleavage sites are predom inantly
dipeptide signals that contain Arg or Lys or both. The presence or absence o f appropriate proteases determ ines the
nature o f the peptides generated from a given precursor. N um bers represent the lengths o f peptides that can be generated
from the precursors.
complements their counterparts in the gastrointestinal tract
(see Chapter 12). For example, cholecystokinin (CCK)
functions in the gut to promote digestion by acting on the
gallbladder and exocrine pancreas. The gut-derived CCK
is a large peptide (33 amino acid residues), the last
8
of
which confer biological activity. In the brain, a smaller
CCK with the same
8
carboxy terminal amino acids func-
tions as a neurotransmitter for appetite suppression. Thus,
in the brain and in the gut, CCK influences some facet
of eating. Gastrin, a 17 residue hormone in the gut that
stimulates gastric acid secretion and that has the same
five carboxy terminal residues as CCK, has also been de-
tected in the brain, where it is believed to have an effect on
appetite.
Endogenous Opiates
Opioid neurotransmitters
in the brain are peptides that
modulate pain perception and/or the reaction to perceived
pain; they include the enkephalins, endorphins, dynor-
phins, and neoendorphins. All exert their effects by bind-
ing to specific types of opiate receptors that are located in
various parts of the CNS, but particularly in those regions
that function in pain perception. Derivatives of opium,
the extract of the poppy
Papaver somniferum,
exert their
analgesic and psychological effects through these opiate
receptors.
The endogenous opiates include /1-endorphin, the
enkephalins
(met-enkephalin and leu-enkephalin), the
dynorphins, and the neoendorphins. All are peptides, vary-
ing in size from 5 to 31 amino acid residues. All have
in common an amino terminus consisting of either of
two pentapeptide sequences: Try-Gly-Gly-Phe-Met (the
met-enkephalin sequence) or Tyr-Gly-Gly-Phe-Leu (the
leu-enkephalin sequence). The fundamental endogenous
opioid peptides are the pentapeptides, met-enkephalin and
leu-enkephalin which function as neurotransmitters in the
CNS.
All of the known endogenous opioids are derived
from three different prohormones: pro-opiomelanocortin
(POMC), proenkephalin A, and proenkephalin B (pro-
dynorphin) (Figure 31-2). The genes encoding these are
expressed in the CNS and in other regions of the body (e.g.,
POMC is also produced in the adrenohypophysis and the
gastrointestinal tract; proenkephalin A is also produced
in the adrenal medulla). What is important is that sites
