sequence CLITNCPRG-amide, and F2, which is
an antiparallel dimer consisting of two such
chains. The sequence similarity of the last five
positions is responsible for the immunological
cross-reactivity with arginine-vasopressin [174].
The venom of marine gastropods of the genus
Conus contains vasopressin-like peptides referred
to as conopressins. The Lys-conopressin-G from
C. geographus has the sequence CFIRNCPKGamide, and the Arg-conopressin-S from C. striatus has the sequence CIIRNCPRG-amide [46].
Homology of these invertebrate peptides with the
hypophysis hormones is not certain; their short
sequences make it difficult to exclude convergent
evolution.
With the exception of the agnathans, all vertebrates possess nentral nonapeptide hormones
in addition to the basic type. Of the cartilaginous
fish, the sharks have aspargtocin or valitocin, the
rays glumitocin, and the chimaeras oxytocin. Isotocin (ichthyotocin) appears to be characteristic
of the bony fish classes Teleostei, Holostei,
Chondrostei and Polypteri; however, as only a
very few members of this extensive group have as
yet been examined, some surprises may be in
store. The lungfish, amphibians, reptiles and
birds all possess mesotocin. The Placentalia have
exclusively oxytocin, as have the South American
marsupials (Didelphidae). However, the three
groups of Australian marsupials (Dasyuridae,
Phalangeridae, Macropdidae) produce mesotocin, and the North American opossum Didelphis
virginiana has both mesotocin and oxytocin. The
occurrence of mesotocin in the marsupials could
be taken as an ancestral sign were it not for the
fact that the even more primitive monotreme species both possess only oxytocin [35]. The higher
molecular weight precursor of the nonapeptides
also includes the sequences for the neurophysins
(NPs). Thus, individual neurons in mammals contain either vasopressin or oxytocin together with
the corresponding NP, although in vitro both
nonapeptides can bind either of the NPs. The
approximately 17-kDa precursors of argininevasopressinIMSEL-NP and oxytocinNLDV-NP
from several mammals have been sequenced via
their cDNA. The prepro-AVPIMSEL-NP is made
up consecutively of the signal peptide (19 amino
acids), arginine-vasopressin (9 amino acids), the
linker peptide Gly-Lys-Arg with the glycine residue for amidation of the terminal-COOH and the
basic amino acids of the cleavage site, the MSELneurophysin (NP-II) (93-95 amino acids), and a
glycopeptide (copeptin) of 38-39 amino acids.
Prepro-OTNLDV-NP is similarly constructed
8.1 Hormones of the Neurohypophysis
291
with the signal sequence, oxytocin (OT), the linker peptide and NI-I, but it has a histidine residue
in place of copeptin [35]. The genes for these precursors are organized into three exons. In the
guinea-pig, an NP glycopeptide fragment results
from incomplete processing of the AVP/NP-II
precursor, an indication that different enzymes
are responsible for the cleavage sites A VP/NP and
NP/glycopeptide. This processing is complete in
the rat, although the sequence of the precursor
differs at only two positions from that of the
guinea-pig [34]. In the vasotocinINP and isotocin/
NP precursors from the teleost Catostomus commersoni and in the duplicated prepro-vasotocin/
NP from Oncorhynchus keta, the NP sequences
have a C-terminal extension of about 30 amino
acids, which, apart from one missing glycosylation site, is very similar to mammalian copeptin
[146]. A new type of neurohypophysis hormone
found in the anurans arises by variant processing
of the vasotocinINP precursor; these hormones
are found only in anurans and are apparently involved in osmoregulation. Hydrin 1
(vasotocinyl-Gly-Lys-Arg) is found in Xenopus
laevis, and hydrin 2 (vasotocinyl-Gly) occurs in
various species of the genera Rana and Bufo
[138, 184] .
The neurophysins are acidic proteins of about
10 kDa with 90-100 amino acids; complete or
partial sequences are known for NPs of various
mammals and of the cod Gadus morrhua.
They are phylogenetically very conservative,
positions 10-74 being practically invariant in the
mammals. The classification suggested by Chauvet in 1976 is based on the occupation of positions 2,3,6 and 7, and distinguishes the MSEL
classes linked to vasopressin and the VLDV
classes belonging to oxytocin. However, the larger amount of material now available for comparison reveals considerable variability, particularly at positions 2 and 3. Whatever the case, the
sequence differences between the .two NP types
are always greater than the species-specific differences within each type. Thus, the gene duplications leading to the appearance of the two
nonapeptide-NP precursors occurred much earlier than the separation of the present mammalian
species [1]. Both NP classes are to be found in
birds. The only sequenced example, from the ostrich, agrees in only 60-65 % of its 93 amino acids
with mammalian neurophysin [116].
an antiparallel dimer consisting of two such
chains. The sequence similarity of the last five
positions is responsible for the immunological
cross-reactivity with arginine-vasopressin [174].
The venom of marine gastropods of the genus
Conus contains vasopressin-like peptides referred
to as conopressins. The Lys-conopressin-G from
C. geographus has the sequence CFIRNCPKGamide, and the Arg-conopressin-S from C. striatus has the sequence CIIRNCPRG-amide [46].
Homology of these invertebrate peptides with the
hypophysis hormones is not certain; their short
sequences make it difficult to exclude convergent
evolution.
With the exception of the agnathans, all vertebrates possess nentral nonapeptide hormones
in addition to the basic type. Of the cartilaginous
fish, the sharks have aspargtocin or valitocin, the
rays glumitocin, and the chimaeras oxytocin. Isotocin (ichthyotocin) appears to be characteristic
of the bony fish classes Teleostei, Holostei,
Chondrostei and Polypteri; however, as only a
very few members of this extensive group have as
yet been examined, some surprises may be in
store. The lungfish, amphibians, reptiles and
birds all possess mesotocin. The Placentalia have
exclusively oxytocin, as have the South American
marsupials (Didelphidae). However, the three
groups of Australian marsupials (Dasyuridae,
Phalangeridae, Macropdidae) produce mesotocin, and the North American opossum Didelphis
virginiana has both mesotocin and oxytocin. The
occurrence of mesotocin in the marsupials could
be taken as an ancestral sign were it not for the
fact that the even more primitive monotreme species both possess only oxytocin [35]. The higher
molecular weight precursor of the nonapeptides
also includes the sequences for the neurophysins
(NPs). Thus, individual neurons in mammals contain either vasopressin or oxytocin together with
the corresponding NP, although in vitro both
nonapeptides can bind either of the NPs. The
approximately 17-kDa precursors of argininevasopressinIMSEL-NP and oxytocinNLDV-NP
from several mammals have been sequenced via
their cDNA. The prepro-AVPIMSEL-NP is made
up consecutively of the signal peptide (19 amino
acids), arginine-vasopressin (9 amino acids), the
linker peptide Gly-Lys-Arg with the glycine residue for amidation of the terminal-COOH and the
basic amino acids of the cleavage site, the MSELneurophysin (NP-II) (93-95 amino acids), and a
glycopeptide (copeptin) of 38-39 amino acids.
Prepro-OTNLDV-NP is similarly constructed
8.1 Hormones of the Neurohypophysis
291
with the signal sequence, oxytocin (OT), the linker peptide and NI-I, but it has a histidine residue
in place of copeptin [35]. The genes for these precursors are organized into three exons. In the
guinea-pig, an NP glycopeptide fragment results
from incomplete processing of the AVP/NP-II
precursor, an indication that different enzymes
are responsible for the cleavage sites A VP/NP and
NP/glycopeptide. This processing is complete in
the rat, although the sequence of the precursor
differs at only two positions from that of the
guinea-pig [34]. In the vasotocinINP and isotocin/
NP precursors from the teleost Catostomus commersoni and in the duplicated prepro-vasotocin/
NP from Oncorhynchus keta, the NP sequences
have a C-terminal extension of about 30 amino
acids, which, apart from one missing glycosylation site, is very similar to mammalian copeptin
[146]. A new type of neurohypophysis hormone
found in the anurans arises by variant processing
of the vasotocinINP precursor; these hormones
are found only in anurans and are apparently involved in osmoregulation. Hydrin 1
(vasotocinyl-Gly-Lys-Arg) is found in Xenopus
laevis, and hydrin 2 (vasotocinyl-Gly) occurs in
various species of the genera Rana and Bufo
[138, 184] .
The neurophysins are acidic proteins of about
10 kDa with 90-100 amino acids; complete or
partial sequences are known for NPs of various
mammals and of the cod Gadus morrhua.
They are phylogenetically very conservative,
positions 10-74 being practically invariant in the
mammals. The classification suggested by Chauvet in 1976 is based on the occupation of positions 2,3,6 and 7, and distinguishes the MSEL
classes linked to vasopressin and the VLDV
classes belonging to oxytocin. However, the larger amount of material now available for comparison reveals considerable variability, particularly at positions 2 and 3. Whatever the case, the
sequence differences between the .two NP types
are always greater than the species-specific differences within each type. Thus, the gene duplications leading to the appearance of the two
nonapeptide-NP precursors occurred much earlier than the separation of the present mammalian
species [1]. Both NP classes are to be found in
birds. The only sequenced example, from the ostrich, agrees in only 60-65 % of its 93 amino acids
with mammalian neurophysin [116].