The effect of neosurugatoxin on the release of neurohypophysial hormones by nicotine, hypotension and an osmotic stimulus in the rat.

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.