A few pharmacodynamic effects of
adrenocorticophic hormone do not stem from its
adrenocortiotropic properties The crisis of
muscular hypertonus (acts of stretching)
observed in dogs, cats, rabbits and rats
injected intracisternally with small doses of
this hormone are probably another example of
pharmacological effects independent of its
adrenorticotropic properties. Although the
behavioural changes following the intracisternal
injection of many other hormonal preparations
were investigated, the modification of muscular
tonus mentioned above is obtained only with
small doses of adrenocorticophic hormone or
melanocyte-stimulating hormone. The term
intracisternal injection indicates the
replacement of liquor drawn from the cisterna
magna with saline in which the various drugs
under investigation are dissolved. The volume of
these injections never exceeded 2 ml. in dogs, 1
ml, in cats and rabbits and 0,1 ml, in rats. The
pH of the injected solutions was made as close
as possible to physiological values.
From Table 1 it can be seen that in the dog
these two hormones were the only ones to induce
the peculiar crisis of increasing muscular tonus
spreading to many different muscular groups and
resulting in generalized act of stretching. In
the dog the stretching crisis, illustrated in
Fig. 1, appears within 1-2 hr. after the
intracisternal injections as a recurrent series
with intermissions of complete recovery and
normal muscular tonus. 4-5 hr after the
injection not only does the crisis persist but
the time between subsequent stretching acts
becomes shorter and shorter so that the onset of
one overlaps the end of the preceding one. This
lasts for 24 hr and more, ending with complete
recovery. This phenomenon appears strictly
dependent on the method of administration, for
the infusion of comparatively large amounts of
melanocytestimulating hormone (1 mgm./kgm.) into
the common carotid artery is ineffective.
Stretching crises may also be seen in cats,
rabbits and rats under the same conditions.
However, a few characteristics may help in
differentiating the symptoms caused by the two
hormones in different animal species. When
melanocyte-stimulating hormone is injected into
the cisterna magna of rabbits a short period of
convulsions precedes a state of catatonic like
stupor. Within 1 hr the latter is interrupted by
a stretching crisis often accompanied by
yawning. A complete recovery occurs within 4-5
hr. Catatonic like stupor occurs in rats,
together with scratching movements of unusually
long duration. In cats the stretching crisis
follows a period of either drowsiness or
catatonic-like stupor. Other symptoms may be
associated with the intracisternal injection of
these two hormones. It is important to mention
that neither rectal temperature (in rabbits) nor
bloodreducing substances (in dogs) vary. In dogs
eosinopaenia and ptyalism and in rabbits a
slight arterial hypotension may occur.
The liquor drawn while the behavioural
changes are in progress does not cause either
the isolated guinea pig ileum or the isolated
rat uterus to contract. Nevertheless the same
liquor if injected intracisternally to another
dog evokes the symptoms described above. In the
latter case the latent period is not shortened
as one would expect. The latent period lasts
longer after injecting either hormone into the
lumbar subaracnoidal space of dogs, but the
symptoms remain unchanged.
Since in dogs adrenalectomy does not curtail
the muscular hypertonus caused by
intracisternally injected adrenocorticotrophic
hormone, this effect cannot be due to its
adrenocorticotropic activities. Moreover in dogs
the intracisternal injection of a number of
drugs causing eosinopaenia (histamine, 0.1;
48/80, 1; serotonin creatine sulphate, 0.1;
1-epinephrine, 0.02; 1-ephedrine, 2;
d-amphetamine, 1; mgm./kgm.) is not followed by
behavioural changes similar to those described
above. Finally, chlorpromazine and reserpine
injected into the cisterna magna of dogs do not
evoke a stretching crisis.
The possible explanations of the mechanism
of this pharmacological activity of
adrenocorticotrophic hormone and
melanocyte-stimulating hormone lack experimental
support. Nevertheless as a working hypothesis I
suggest that the polypeptide chain common to
both hormones is either directly or indirectly
involved.
