202
RACHMIEL LEVINE
III. ADRENALINE
The adrenal medulla manufactures and releases two closely related,
hormonally active amines, epinephrine and norepinephrine. The known
effects of these materials on various organs and tissues are so numerous
and varied, that it would be unrewarding to try and attempt to get an
insight into some basic action underlying all of the observed phenomena.
We shall therefore select one conspicuous and functionally significant
effect of adrenaline, the rise in the blood sugar level, for the more detailed survey. It has been amply demonstrated over the years that this is
a regulatory action of adrenaline, since a release of the hormone from
the gland is brought about by lowering the blood sugar (WeilMalherbe, 1955).
The hyperglycemic effect of adrenaline depends upon the presence
of an adequate amount of liver glycogen. After prolonged fasting, when
the liver glycogen store is almost completely depleted, adrenaline no
longer raises blood sugar levels. The known enzymatic mechanisms by
which glucose is released to the blood and derived from the hepatic
glycogen stores are presented in Fig. 11. The problem before us is
the question: on which of these reactions does adrenaline directly or
indirectly exert its influence? Many years ago it was demonstrated that
simultaneously with the rise in blood sugar there was also a rise in blood
lactic acid, following adrenaline release or administration. This response
pointed to an action on muscle glycogen (Reisser, 1947; Tuerkischer and
Wertheimer, 1948; Walaas and Walaas, 1950), an action which was
proven by an analysis of muscle for glycogen, hexose phosphates, and
lactic acid. The reason adrenaline leads to a release of lactic acid in
muscle is because this tissue does not contain the specific glucose-6phosphatase and therefore cannot give rise to free glucose when its
glycogen is being broken down (Fig. 11). Taken together, these data
indicate that adrenaline must influence one or more of the reactions
common to both liver and muscle, but could not exert its action on the
glucose-6-phosphatase reaction, which does not exist in muscle.
The studies of Sutherland and his co-workers began with these considerations and have carried the problem ahead to its present state
(Sutherland and Cori, 1951a, b; Sutherland, 1952; Wosilait and Sutherland, 1956; Rail et al., 1956). The system used consists of liver and
muscle slices in vitro-, most of the data were obtained with liver. The
experimental observations and the conclusions drawn may be summarized
as follows:
1. Neither the glucose-6-phosphatase system nor the phosphoglucomutase system, which converts glucose-6-phosphate to glucose-l-phos-
RACHMIEL LEVINE
III. ADRENALINE
The adrenal medulla manufactures and releases two closely related,
hormonally active amines, epinephrine and norepinephrine. The known
effects of these materials on various organs and tissues are so numerous
and varied, that it would be unrewarding to try and attempt to get an
insight into some basic action underlying all of the observed phenomena.
We shall therefore select one conspicuous and functionally significant
effect of adrenaline, the rise in the blood sugar level, for the more detailed survey. It has been amply demonstrated over the years that this is
a regulatory action of adrenaline, since a release of the hormone from
the gland is brought about by lowering the blood sugar (WeilMalherbe, 1955).
The hyperglycemic effect of adrenaline depends upon the presence
of an adequate amount of liver glycogen. After prolonged fasting, when
the liver glycogen store is almost completely depleted, adrenaline no
longer raises blood sugar levels. The known enzymatic mechanisms by
which glucose is released to the blood and derived from the hepatic
glycogen stores are presented in Fig. 11. The problem before us is
the question: on which of these reactions does adrenaline directly or
indirectly exert its influence? Many years ago it was demonstrated that
simultaneously with the rise in blood sugar there was also a rise in blood
lactic acid, following adrenaline release or administration. This response
pointed to an action on muscle glycogen (Reisser, 1947; Tuerkischer and
Wertheimer, 1948; Walaas and Walaas, 1950), an action which was
proven by an analysis of muscle for glycogen, hexose phosphates, and
lactic acid. The reason adrenaline leads to a release of lactic acid in
muscle is because this tissue does not contain the specific glucose-6phosphatase and therefore cannot give rise to free glucose when its
glycogen is being broken down (Fig. 11). Taken together, these data
indicate that adrenaline must influence one or more of the reactions
common to both liver and muscle, but could not exert its action on the
glucose-6-phosphatase reaction, which does not exist in muscle.
The studies of Sutherland and his co-workers began with these considerations and have carried the problem ahead to its present state
(Sutherland and Cori, 1951a, b; Sutherland, 1952; Wosilait and Sutherland, 1956; Rail et al., 1956). The system used consists of liver and
muscle slices in vitro-, most of the data were obtained with liver. The
experimental observations and the conclusions drawn may be summarized
as follows:
1. Neither the glucose-6-phosphatase system nor the phosphoglucomutase system, which converts glucose-6-phosphate to glucose-l-phos-