Tetrodotoxin-sensitive release of adrenaline, noradrenaline and neuropeptide Y-like immunoreactivity in the pithed guinea-pig in the absence of electrical preganglionic nerve stimulation

Abstract

The effect of tetrodotoxin (TTX) on plasma noradrenaline (NA), adrenaline (A) and neuropeptide Y-like immunoreactivity (NPY-LI) levels was evaluated in the pithed guinea pig, in the absence of electrical stimulation and following preganglionic nerve stimulation (PNS). Blood samples for determination of NA, A and NPY-LI were collected 5 min before and 5 min after injection of saline (control group, n = 6) or TTX (13 μg/kg, i.v., TTX-treated group, n = 8), respectively. In both groups, blood samples were collected 20 s and 40 s after initiation of PNS. In the absence of electrical stimulation, TTX reduced the plasma NA level by 66%, NPY-LI level by 42%, whereas the plasma A level was not significantly altered by the neurotoxin. In the control group, PNS elicited a 27-fold increase of plasma NA, a 60-fold increase of plasma A and enhanced the NPY-LI levels by 13%. Pretreatment with TTX completely blocked this release of sympathetic transmitters. The present results suggest that a certain degree of spontaneous nerve activity is present in the pithed animal model, also during baseline conditions, since TTX significantly reduced NA and NPY-LI in the absence of electrical stimulation. This spontaneous nerve activity is probably a consequence of local mechanical activity of the pithing rod capable of eliciting action potentials at the preganglionic level of the sympathetic nerve terminals.