Presynaptic nicotinic acetylcholine receptors in the myenteric plexus of guinea pig intestine

Presynaptic nicotinic acetylcholine receptors (nAChRs) were studied in myen teric plexus preparations from guinea pig ileum using intracellular electro physiological methods. Microapplication of nicotine (1 mM) caused a biphasi c depolarization in all AH neurons (n = 30) and in 36 of 49 S neurons. Cyti sine (1 mM) caused fast depolarizations in S neurons and no response in AH neurons. Mecamylamine (10 mu M) blocked all responses caused by nicotine an d cytisine. TTX (0.3 mu M) blocked slow excitatory synaptic potentials in S and AH neurons but had no effect on fast depolarizations caused by nicotin e. Nicotine-induced slow depolarizations were reduced by TTX in two of twel ve AH neurons (79% inhibition) and four of nine S neurons (90 +/- 12% inhib ition). Slow nicotine-induced depolarizations in the remaining neurons were TTX resistant. TTX-resistant slow depolarizations were inhibited after neu rokinin receptor 3 desensitization caused by senktide (0.1 mu M); senktide desensitization inhibited the slow nicotine-induced depolarization by 81 +/ - 5% and 63 +/- 15% in AH and S neurons, respectively. A low-calcium and hi gh-magnesium solution blocked nicotine-induced slow depolarizations in AH n eurons. In conclusion, presynaptic nAChRs mediate the release of substance P and/or neurokinin A to cause slow depolarizations of myenteric neurons.