2. THE NEUROHYPOPHYSIS
135
clavata, and Raia batis. The activities were relatively weak. The oxytocic
activities ranged between 7.0 and 54.2 mU/mg acetone dried powder,
and the highest value so far reported is only 58.5 f 10.8 mU/mg, for
Dasyatis sabinu (Perks, 1966). Pressor effects could not be detected. The
active agents were distributed preferentially in the neurointennediate
lobe. They shared with oxytocin inactivation by sodium thioglycollate,
sodium hydroxide, ultraviolet light, and chymotrypsin ( Perks and Dodd,
1963a,b). In contrast to the mammalian vasopressins, the elasmobranch
oxytocic agent was resistant to trypsin, and therefore it was unlikely to
contain arginine or lysine. Despite the general parallel with the properties
of oxytocin, there were quantitative differences in the ratios of different
biological activities. In Squalus acanthias, Scyliorhinus caniculus, Raia
clavata, R. batis, Dasyatis sabina, Sphyrna mokarran, Eulunia milbe&
and Carchurinus kucas the ratios of milk-ejection : oxytocic : antidiuretic
activities were relatively consistent, and averaged 3.4: 1 : 0.03 ( Perks et al.,
1960; Perks and Dodd, 1963a; Perks, 1966). This contrasted with ratios of
approximately unity for mammalian (ox) pituitary powders, and of
1 : 1 : 0.0067 for synthetic oxytocin (van Dyke et al., 1955). This discrepancy between the elasmobranch and mammalian extracts was confirmed
in Squalus acanthias by W. H. Sawyer et al. (1961). These workers extended the activities which could be found in the extract to avian depressor activity, frog bladder activity, and stimulation of the hen oviduct. In
addition, they detected a weak pressor effect; although no pressor activity
had been found by Perks et al. (1960; Perks and Dodd, 1963a) in their
earlier experiments, it is probable that this was masked by the strong
vasodepressor substances which were present in their extracts. Sawyer
and his co-workers found a twofold potentiation of the oxytocic effect by
the presence of magnesium ions; again, this indicated the presence of a
peptide other than oxytocin. It was clear that the elasmobranchs contained a new oxytocinlike principle of high milk-ejection potency, free,
or nearly free, of any vasopressor peptide: This was the first demonstration of a naturally occurring, neutral analog of oxytocin (Perks et al.,
1960; W. H. Sawyer et aZ., 1961).
The pharmacological studies left the possibility that the observed
activities could be the result of a mixture of oxytocinlike peptides. Heller
and his co-workers attempted to resolve this possibility by paper chromatography. They subjected extracts from Squalus acanthias, Scyliorhinus
caniculus, Raia clavata, and Negaprion breuirostris to paper chromatography in butanol: acetic acid: water, 4 : 1 : 5 ( Heller and Pickering, 1961;
Heller and Roy, 1965a,b). The oxytocic activities were resolved into two
peaks. The first was a fast-running component, designated “E2.” It represented the major oxytocic component of the elasmobranch pituitary, and
135
clavata, and Raia batis. The activities were relatively weak. The oxytocic
activities ranged between 7.0 and 54.2 mU/mg acetone dried powder,
and the highest value so far reported is only 58.5 f 10.8 mU/mg, for
Dasyatis sabinu (Perks, 1966). Pressor effects could not be detected. The
active agents were distributed preferentially in the neurointennediate
lobe. They shared with oxytocin inactivation by sodium thioglycollate,
sodium hydroxide, ultraviolet light, and chymotrypsin ( Perks and Dodd,
1963a,b). In contrast to the mammalian vasopressins, the elasmobranch
oxytocic agent was resistant to trypsin, and therefore it was unlikely to
contain arginine or lysine. Despite the general parallel with the properties
of oxytocin, there were quantitative differences in the ratios of different
biological activities. In Squalus acanthias, Scyliorhinus caniculus, Raia
clavata, R. batis, Dasyatis sabina, Sphyrna mokarran, Eulunia milbe&
and Carchurinus kucas the ratios of milk-ejection : oxytocic : antidiuretic
activities were relatively consistent, and averaged 3.4: 1 : 0.03 ( Perks et al.,
1960; Perks and Dodd, 1963a; Perks, 1966). This contrasted with ratios of
approximately unity for mammalian (ox) pituitary powders, and of
1 : 1 : 0.0067 for synthetic oxytocin (van Dyke et al., 1955). This discrepancy between the elasmobranch and mammalian extracts was confirmed
in Squalus acanthias by W. H. Sawyer et al. (1961). These workers extended the activities which could be found in the extract to avian depressor activity, frog bladder activity, and stimulation of the hen oviduct. In
addition, they detected a weak pressor effect; although no pressor activity
had been found by Perks et al. (1960; Perks and Dodd, 1963a) in their
earlier experiments, it is probable that this was masked by the strong
vasodepressor substances which were present in their extracts. Sawyer
and his co-workers found a twofold potentiation of the oxytocic effect by
the presence of magnesium ions; again, this indicated the presence of a
peptide other than oxytocin. It was clear that the elasmobranchs contained a new oxytocinlike principle of high milk-ejection potency, free,
or nearly free, of any vasopressor peptide: This was the first demonstration of a naturally occurring, neutral analog of oxytocin (Perks et al.,
1960; W. H. Sawyer et aZ., 1961).
The pharmacological studies left the possibility that the observed
activities could be the result of a mixture of oxytocinlike peptides. Heller
and his co-workers attempted to resolve this possibility by paper chromatography. They subjected extracts from Squalus acanthias, Scyliorhinus
caniculus, Raia clavata, and Negaprion breuirostris to paper chromatography in butanol: acetic acid: water, 4 : 1 : 5 ( Heller and Pickering, 1961;
Heller and Roy, 1965a,b). The oxytocic activities were resolved into two
peaks. The first was a fast-running component, designated “E2.” It represented the major oxytocic component of the elasmobranch pituitary, and