8.2.2 Peptides from the Hypothalamus, Gut and Frog Skin
293
found in teleosts and birds. Two GnRFs are
known in the chicken, of which type I shows one
difference to the mammalian GnRF and type II
shows three differences. Whereas chicken GnRFs
give reduced receptor binding and hormone
release in rats, the chicken receptors react to
mammalian GnRF to the same degree as to their
own factor [249]. GnRF-like substances have
been detected immunologically in the tunicate
Ciona intestinalis but not in either crustaceans or
platyhelminthes. The a mating factor of yeast
coincides in 6 of its 13 amino acids with mammalian GnRF, binds to rat receptors and releases
hormone from the rat hypophysis [249]. The
human GnRF precursor consists of a signal peptide (23 amino acids), QnRF (10 amino acids),
linker peptide Gly-Lys-Arg, and a C-terminal
sequence of 56 amino acids [249].
Somatostatin is a peptide of 14 amino acids
(Fig. 8.2c) that inhibits the release of growth hormone, TRF and other hormones. SST-14 is highly
conservative, the same sequence being present
from the agnathan Myxine to the mammals. The
only known exception was found in two primitive
fish species: 5-Asn to Ser in the Pacific ratfish
Hydrolagus colliei (Holocephali), and 12-Thr to
Ser in the lamprey Petromyzon marinus (Agnatha) [4,41]. SST-14-like substances have been
detected immunologically in tunicates and insects
and even in the ciliate Tetrahymena and in E. coli.
In mammals, both SST-14 and SST-28, with 28
amino acids, are produced from the same SST;
the relative proportions of the two products in the
hypothalamus, gut and pancreas vary. Fish also
contain larger SSTs with 22-37 amino acids; however, these do not arise by the tissue-specific processing of the same gene product but are encoded
by a further gene. Detailed investigations of the
angler fish Lophius piscatorius showed that
gene I produces the conservative SST-14 and gene II the SST-28, which is in part hydroxylated on
23-Lys [144].
Corticotropin-releasing factor, which stimulates the secretion of adrenocorticotropins and /3endorphins, is a peptide of 41 amino acids
(Fig. 8.2 d); the human and rat sequences coincide but differ from that of the sheep in seven
positions. It is noteworthy that the CRF sequence
of the teleost Catostomus commersoni differs
from the human and rat sequences in only two
positions at the C-terminus [159]. CRF agrees to
a certain extent with sauvagin (40 amino acids)
from the skin of the South American frog Phyllomedusa sauvagei, and with urotensin-I from the
urophysis of various teleosts [35]. Growthhormone-releasing factors have been isolated
from the hypothalamus of various mammalian
species and have been sequenced. They are peptides of 44 amino acids which are C-terminal amidated and only vary slightly in the C-terminal
region. They stimulate the release of growth hormone, i.e. they are antagonists of the SSTs. Mammalian GRFs also function in fish and GRF-like
substances have been detected immunologically
in the salmon Oncorhyncus keta and O. kisutch
[129]. The GRFs belong to the glucagon-secretin
family. Rat GRF is unusual in that it is only 43
amino acids long, is not ami dated at the Cterminus and differs from human GRF in no less
than 14 positions. Human GRF causes the release
of growth hormone in both birds and fish
[123, 249].
8.2.2 Peptides from the Hypothalamus,
Gut and Frog Skin
Peptides of rather similar structure are found in
the hypothalamus and other parts of the central
nervous system (CNS), in the gut wall and the
pancreas, and in the skin of various frogs. This
surprising discovery has been rationalized in that
gut neurons and skin glands both arise from cells
of the neural groove, which is replaced by the
neural tube during embryo development. These
substances may be grouped around neurotransmitters or neuromodulators, like substance P, and
the neurotensins [14]. Substance P (SP) is an
undecapeptide (Fig. 8.2 e) found especially in the
hypothalamus, although it also occurs in other
parts of the CNS and in the first part of the small
intestine; it is released as a transmitter by painconducting nerve fibres. This is the bestinvestigated representative of the tachykinins,
which are characterized by the C-terminal
sequence -FXGLM-amide [153]. Alternative
splicing of the products of the SP-precursor gene
results in several prepro-tachykinins, each of
which, apart from SP, contains other tachykinin
sequences [74]. The same peptide family includes
various species-specific peptides found at high
concentrations in the skin of anurans, e.g. physalaemin from Physalaemus fuscumaculatus, or the
four ranatachykinins from Rana catesbeiana
[109]; other examples are scyliorhinins from the
gut of the shark Scyliorhinus canicula [39], and
eledoisin from the salivary glands of the cephalopod Eledone moschata (Fig. 8.2). Physalaeminlike peptides from rabbit stomach have also been
isolated and sequenced [233]. Bombesin, from
293
found in teleosts and birds. Two GnRFs are
known in the chicken, of which type I shows one
difference to the mammalian GnRF and type II
shows three differences. Whereas chicken GnRFs
give reduced receptor binding and hormone
release in rats, the chicken receptors react to
mammalian GnRF to the same degree as to their
own factor [249]. GnRF-like substances have
been detected immunologically in the tunicate
Ciona intestinalis but not in either crustaceans or
platyhelminthes. The a mating factor of yeast
coincides in 6 of its 13 amino acids with mammalian GnRF, binds to rat receptors and releases
hormone from the rat hypophysis [249]. The
human GnRF precursor consists of a signal peptide (23 amino acids), QnRF (10 amino acids),
linker peptide Gly-Lys-Arg, and a C-terminal
sequence of 56 amino acids [249].
Somatostatin is a peptide of 14 amino acids
(Fig. 8.2c) that inhibits the release of growth hormone, TRF and other hormones. SST-14 is highly
conservative, the same sequence being present
from the agnathan Myxine to the mammals. The
only known exception was found in two primitive
fish species: 5-Asn to Ser in the Pacific ratfish
Hydrolagus colliei (Holocephali), and 12-Thr to
Ser in the lamprey Petromyzon marinus (Agnatha) [4,41]. SST-14-like substances have been
detected immunologically in tunicates and insects
and even in the ciliate Tetrahymena and in E. coli.
In mammals, both SST-14 and SST-28, with 28
amino acids, are produced from the same SST;
the relative proportions of the two products in the
hypothalamus, gut and pancreas vary. Fish also
contain larger SSTs with 22-37 amino acids; however, these do not arise by the tissue-specific processing of the same gene product but are encoded
by a further gene. Detailed investigations of the
angler fish Lophius piscatorius showed that
gene I produces the conservative SST-14 and gene II the SST-28, which is in part hydroxylated on
23-Lys [144].
Corticotropin-releasing factor, which stimulates the secretion of adrenocorticotropins and /3endorphins, is a peptide of 41 amino acids
(Fig. 8.2 d); the human and rat sequences coincide but differ from that of the sheep in seven
positions. It is noteworthy that the CRF sequence
of the teleost Catostomus commersoni differs
from the human and rat sequences in only two
positions at the C-terminus [159]. CRF agrees to
a certain extent with sauvagin (40 amino acids)
from the skin of the South American frog Phyllomedusa sauvagei, and with urotensin-I from the
urophysis of various teleosts [35]. Growthhormone-releasing factors have been isolated
from the hypothalamus of various mammalian
species and have been sequenced. They are peptides of 44 amino acids which are C-terminal amidated and only vary slightly in the C-terminal
region. They stimulate the release of growth hormone, i.e. they are antagonists of the SSTs. Mammalian GRFs also function in fish and GRF-like
substances have been detected immunologically
in the salmon Oncorhyncus keta and O. kisutch
[129]. The GRFs belong to the glucagon-secretin
family. Rat GRF is unusual in that it is only 43
amino acids long, is not ami dated at the Cterminus and differs from human GRF in no less
than 14 positions. Human GRF causes the release
of growth hormone in both birds and fish
[123, 249].
8.2.2 Peptides from the Hypothalamus,
Gut and Frog Skin
Peptides of rather similar structure are found in
the hypothalamus and other parts of the central
nervous system (CNS), in the gut wall and the
pancreas, and in the skin of various frogs. This
surprising discovery has been rationalized in that
gut neurons and skin glands both arise from cells
of the neural groove, which is replaced by the
neural tube during embryo development. These
substances may be grouped around neurotransmitters or neuromodulators, like substance P, and
the neurotensins [14]. Substance P (SP) is an
undecapeptide (Fig. 8.2 e) found especially in the
hypothalamus, although it also occurs in other
parts of the CNS and in the first part of the small
intestine; it is released as a transmitter by painconducting nerve fibres. This is the bestinvestigated representative of the tachykinins,
which are characterized by the C-terminal
sequence -FXGLM-amide [153]. Alternative
splicing of the products of the SP-precursor gene
results in several prepro-tachykinins, each of
which, apart from SP, contains other tachykinin
sequences [74]. The same peptide family includes
various species-specific peptides found at high
concentrations in the skin of anurans, e.g. physalaemin from Physalaemus fuscumaculatus, or the
four ranatachykinins from Rana catesbeiana
[109]; other examples are scyliorhinins from the
gut of the shark Scyliorhinus canicula [39], and
eledoisin from the salivary glands of the cephalopod Eledone moschata (Fig. 8.2). Physalaeminlike peptides from rabbit stomach have also been
isolated and sequenced [233]. Bombesin, from