Effects of nicotine receptor agonists on acetylcholine release from the isolated motor nerve, small intestine and trachea of rats and guinea-pigs

Abstract

The effects of nicotine receptor agonists on the release of [3H]acetylcholine from the phrenic nerve, the small intestine and the trachea were investigated to characterize neuronal nicotine receptors within the peripheral nervous system. Contraction of the indirectly-stimulated hemidiaphragm was recorded to investigate desensitization of the postsynaptic muscular nicotine receptors. Nicotine, cytisine, 1,1-dimethyl-4-phenylpiperazinium and 2-(4-aminophenyl)-ethyl-trimethyl-ammoniumiodide caused a concentration-dependent (0.1-30 microM) increase in evoked [3H]acetylcholine release from the phrenic nerve, whereby bell-shaped concentration-response curves were obtained. The rank order of decreasing potency was: nicotine greater than cytisine greater than 1,1-dimethyl-4-phenylpiperazinium greater than 2-(4-aminophenyl)-ethyl-trimethyl-ammoniumiodide. The presynaptic effects of nicotine depended strongly on the exposure time: facilitation occurred after a short 20 s exposure and inhibition after a 3 min exposure, whereas nicotine no longer affected evoked [3H]acetylcholine release after a 15 min exposure. Pre-exposure (40 min) of the phrenic nerve to 0.3 microM nicotine prevented any subsequent modulatory effect of a high nicotine concentration. In contrast, the contraction of the indirectly-stimulated hemidiaphragm remained unaffected in the presence of 0.3-30 microM nicotine, but a concentration of 1 mM nicotine abolished skeletal muscle contraction. Nicotine (10 microM) produced a substantial release of [3H]acetylcholine in the small intestine but not in the isolated trachea. The present experiments show presynaptic nicotine receptors at the phrenic nerve, which, under appropriate conditions, can mediate facilitation of evoked transmitter release. These neuronal receptors appear more sensitive to desensitizing conditions than the postsynaptic muscular nicotine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro exposure to nicotine induces endocytosis of presynaptic AMPA receptors modulating dopamine release in rat nucleus accumbens nerve terminals

“…It is well known that nAChRs are present on nerve terminals and elicit exocytotic release of various neurotransmitters including NA, DA, ACh and GABA in a Ca 2þ dependent manner (Wonnacott et al, 1989;Levin, 1992;Wessler et al, 1992;Guo et al, 1998;Li et al, 1998;Zappettini et al, 2011;Wilkie et al, 1996;Sershen et al, 1997). The finding that the nicotineinduced release of [ 3 H]-NA the release was tetrodotoxin sensitive (Sershen et al, 1997) has been explained by local depolarization and subsequent generation of action potentials further supporting the presence of these receptors on the nerve endings.…”

Ultrastructural Distribution of the α7 Nicotinic Acetylcholine Receptor Subunit in Rat Hippocampus

“…Key words: acetylcholine receptors; nicotine; dendritic spines; postsynaptic density; immuno-electron microscopy; glutamate; GABA; A␤ Acetylcholine (ACh) is the major excitatory neurotransmitter in the peripheral nervous system. Ionotropic nicotinic receptors mediate postsynaptic excitatory responses at the neuromuscular junction, and there is evidence that nicotinic receptors may also act presynaptically to modulate acetylcholine release in the periphery (Wessler et al, 1992;Liang and Vizi, 1997). In the mammalian CNS, specific receptors for nicotinic ligands have been recognized for many years (Arimatsu et al, 1978;Dudai and Segal, 1978;Hunt and Schmidt, 1978;Segal et al, 1978), but only recently has evidence begun to emerge for their functional roles, including possible mediation of fast postsynaptic responses at certain brain sites (Zhang et al, 1993;Roerig et al, 1997;Chu et al, 2000) and modulation of release of various transmitters, including glutamate (Vidal and Changeux, 1993;McGehee et al, 1995;Gray et al, 1996), GABA (Lena et al, 1993), ACh (McGehee et al, 1995), and dopamine (Rapier et al, 1988).…”

Muscarinic cholinergic signaling in cervical cancer cells affects cell motility via ERK1/2 signaling

“…We are not concerned that we did not detect the choline transporter CHT1, which is needed for neuronal ACh synthesis, as there are a number of plasma membrane choline transporters available in nonneuronal cells such as choline transporter-like (CTL1) proteins or organic cation transporters (OCT) 1, 2 and 3, that were not examined in our study (Kummer et al, 2008). mAChRs may contribute to carcinogenic pathways due to increased ACh release after stimulation of nAChRs (Wessler et al, 1992). Muscarinic and nicotinic cholinergic signaling could therefore synergize during cervical carcinogenesis, as discussed for the autocrine effects of ACh by lung cancers.…”