In dogs, intracisternal injections of highly
purified ACTH preparations induce typical,
prolonged, and repeated stretching crises.
Similar effects are caused by purified MSH
preparations and by solutions of ACTH made with
NaOH N/10 treated at 100°C for 20 min.
These findings suggest that the chemical groups
eliciting the stretching responses are related
with those stimulating melanocytes. This
correlation is supported by results obtained
with dogs given intracisternally the acetate
salt of the synthetic hexapeptide H Glu
(NH2)-His-Phe-Arg-Try- Gly-OH with MSH-like
activity. 750 ¶kg or less of this peptide (given
intracisternally) evoke stretching responses
similar to those following injections of MSH or
ACTH. 1.5 mg/kg of the peptide causes lasting
depression and scialorrhea but not a stretching
crisis.
The melanocyte stimulating effect of the
peptide is 2 x 10 5/g; that of a purified MSH
preparation (732179 A by Armour Laboratories,
Chicago) 5 x 108 U/g. The threshold dose for the
stretching response was respectively 500 and 5
¶/kg: indeed these two different pharmacological
actions are strictly related. The hexapeptide,
but not MSH, shows a paradoxycal behaviour and a
pharmacological response evoked by the
polypeptide may change qualitatively with
respect to the dose given intracisternally.
The Figure illustrates a typical stretching
crisis in a dog injected intracisternally with
the hexapeptide.