STIMULATION OF NEUROPEPTIDE RELEASE FROM SENSORY AND ENTERIC NEURONS IN THE GUINEA-PIG BY ALPHA-LATROTOXIN

alpha-Latrotoxin, from black widow spider venom, stimulates exocytosis of small synaptic vesicles at central and peripheral synapses. Howeve r, it is widely accepted that neuropeptide-containing large dense-core vesicles are insensitive to the toxin. In the present study, we inves tigated whether alpha-latrotoxin releases neuropeptides from primary a fferent and enteric neurons. The guinea-pig renal pelvis is innervated by primary sensory neurons containing tachykinins and calcitonin gene -related peptide, but has no functional cholinergic or noradrenergic m otor innervation. alpha-Latrotoxin increased the amplitude of spontane ous myogenic contractions of the renal pelvis, and this effect was pre vented by prior capsaicin desensitization and by antagonists at neurok inin-1 and neurokinin-2 receptors. In the presence of the latter antag onists, alpha-latrotoxin decreased the amplitude of the contractions, and this is likely to be mediated by calcitonin gene-related peptide. Thus, alpha-latrotoxin releases tachykinins and calcitonin gene-relate d peptide from capsaicin-sensitive sensory neurons in the renal pelvis . The circular muscle of the guinea-pig distal colon is innervated by excitatory and inhibitory motor neurons, which use a number of transmi tters. In the presence of antagonists to block each of the known trans mitters apart from the tachykinins, alpha-latrotoxin increased the amp litude of spontaneous contractions; this effect was prevented by the p rior addition of neurokinin-1 and neurokinin-2 receptor antagonists. T hus, alpha-latrotoxin stimulates the release of tachykinins from excit atory motor neurons in the myenteric plexus of the distal colon. In co nclusion, this study demonstrates that alpha-latrotoxin is able to evo ke the release of neuropeptides from both sensory and enteric neurons. This suggests that exocytosis of large dense-core vesicles shares mor e of the features of exocytosis of small synaptic vesicles than has pr eviously been appreciated.