1. Experiments were carried out to test whether
neosurugatoxin (NSTX) which blocks autonomic ganglia also acts centrally, like
hexamethonium, on nicotinic
cholinoceptors involved in the neural control of release of
vasopressin and
oxytocin from the neurohypophysis. 2. In the water-loaded rat under
ethanol anaesthesia,
nicotine 100 micrograms i.v. produced a pressor and an antidiuretic response accompanied by an increase in the urinary excretion of
vasopressin and of
oxytocin-like radioimmunoreactivity (OLRI). This indicates release of both
vasopressin and
oxytocin. 3. Under conditions in which tachyphylaxis was avoided, NSTX, 80 ng i.c.v., caused a prolonged inhibition of the release of both
hormones by
nicotine. 4. NSTX i.c.v. caused some reduction in the pressor response to
nicotine. It is suggested that this response involves both central and peripheral stimulation of the sympathetic nervous system and that the central component is blocked by
neosurugatoxin. 5.
Muscarine, 40 ng i.c.v., produced a pressor and an antidiuretic response with increased urinary excretion of
vasopressin and OLRI. All these effects were blocked by
atropine but were not inhibited by NSTX. 6.
Sodium nitroprusside (SN), 200 micrograms i.v., and hypertonic saline (HS; 1.54 M NaCl
solution) 4 microliters i.c.v., both produced antidiuretic responses accompanied by increased urinary excretion of
vasopressin and OLRI. The ratio of the excretion of
vasopressin to that of OLRI was 5.1 +/- 1.3 (mean +/- s.e.: n = 8) for SN and 1.2 +/- 0.24 (mean +/- s.e.: n = 6) for HS.NSTX 80 ng i.c.v., caused a significant reduction in the antidiuretic response to the
hypotension induced with SN: the increased urinary excretion of
vasopressin was also significantly reduced but not that of OLRI. NSTX had no effect on the response to HS.7. We conclude that NSTX acts centrally on nicotinic
cholinoceptors to block the release of
vasopressin and
oxytocin by
nicotine and the release of
vasopressin, but not that of
oxytocin, by
hypotension. It does not inhibit the release of either
hormone by a central osmotic stimulus.