678
H O N O R B . F E L L A N D L . M . R I N A L D I N I
D . T H E S P E C I F I C I T Y OF T H E A C T I O N OF V I T A M I N A O N
O R G A N C U L T U R E S
It was important to see whether the effects of vitamin A described
above, had specific structural requirements at the molecular level, and
if so, whether these requirements were the same as those for preventing
vitamin A-deficiency in the body. The effects of a series of compounds
related to vitamin A were therefore investigated on organ cultures
of different types.
Epithelia. Glover and Fell (unpublished) studied the action of a
number of compounds on explants ofthe metatarsal skin from 13-day
chick embryos. They found that vitamin A acid was even more potent
in producing mucous metaplasia than vitamin A (alcohol). The ester
of the acid was also very active. Retinene was effective but was transformed by the tissue into vitamin A.
The following compounds related to vitamin A had no action:
citral (Aydelotte, 1963a), j8-ionylidene ethanol, 4-Apo-j8-carotenol and
4-Apo-/?-carotenal (New and Lucy, unpublished).
Cartilage. Fell, Dingle and Webb (1962) compared the effects of a
range of compounds on explants of the cartilaginous limb-bone rudiments of 7-day chick embryos. In a concentration of 0-01 /xmoles/ml
of culture medium, vitamin A acid again was at least as potent as
vitamin A. Vitamin A epoxide, hydrogenated vitamin A, anhydrous
vitamin A, /5-ionone and phytol had no significant effect; at a tenfold
increase in concentration, hydrogenated vitamin A and ^-ionone slightly
reduced the growth in length of the rudiments, but produced no other
significant change.
From these results it is seen that the effect of vitamin A on both
epithelia and cartilage have specific requirements of molecular
structure and that these requirements correspond closely with those
for the inhibition of vitamin A-deficiency in animals.
E. M O D E OF A C T I O N OF V I T A M I N A ON O R G A N C U L T U R E S
The experiments on cartilage in culture shed some light on the mode
of action of vitamin A on this tissue. The resemblance between the
effect of papain protease and of vitamin A on cartilage matrix, suggested that the vitamin might act by enhancing the activity of hydrolytic
enzymes produced by the chondrocytes. This view was supported by
the results of subsequent experiments which showed that exposure to
vitamin A greatly increased the proteolytic activity of cartilage. The
protease released by the explants had an acid p H optimum indicating
that it was probably a cathepsin.
T o pursue the matter further, it was necessary to turn to methods
H O N O R B . F E L L A N D L . M . R I N A L D I N I
D . T H E S P E C I F I C I T Y OF T H E A C T I O N OF V I T A M I N A O N
O R G A N C U L T U R E S
It was important to see whether the effects of vitamin A described
above, had specific structural requirements at the molecular level, and
if so, whether these requirements were the same as those for preventing
vitamin A-deficiency in the body. The effects of a series of compounds
related to vitamin A were therefore investigated on organ cultures
of different types.
Epithelia. Glover and Fell (unpublished) studied the action of a
number of compounds on explants ofthe metatarsal skin from 13-day
chick embryos. They found that vitamin A acid was even more potent
in producing mucous metaplasia than vitamin A (alcohol). The ester
of the acid was also very active. Retinene was effective but was transformed by the tissue into vitamin A.
The following compounds related to vitamin A had no action:
citral (Aydelotte, 1963a), j8-ionylidene ethanol, 4-Apo-j8-carotenol and
4-Apo-/?-carotenal (New and Lucy, unpublished).
Cartilage. Fell, Dingle and Webb (1962) compared the effects of a
range of compounds on explants of the cartilaginous limb-bone rudiments of 7-day chick embryos. In a concentration of 0-01 /xmoles/ml
of culture medium, vitamin A acid again was at least as potent as
vitamin A. Vitamin A epoxide, hydrogenated vitamin A, anhydrous
vitamin A, /5-ionone and phytol had no significant effect; at a tenfold
increase in concentration, hydrogenated vitamin A and ^-ionone slightly
reduced the growth in length of the rudiments, but produced no other
significant change.
From these results it is seen that the effect of vitamin A on both
epithelia and cartilage have specific requirements of molecular
structure and that these requirements correspond closely with those
for the inhibition of vitamin A-deficiency in animals.
E. M O D E OF A C T I O N OF V I T A M I N A ON O R G A N C U L T U R E S
The experiments on cartilage in culture shed some light on the mode
of action of vitamin A on this tissue. The resemblance between the
effect of papain protease and of vitamin A on cartilage matrix, suggested that the vitamin might act by enhancing the activity of hydrolytic
enzymes produced by the chondrocytes. This view was supported by
the results of subsequent experiments which showed that exposure to
vitamin A greatly increased the proteolytic activity of cartilage. The
protease released by the explants had an acid p H optimum indicating
that it was probably a cathepsin.
T o pursue the matter further, it was necessary to turn to methods