93
6
Take-Home Message
5 Aconitine from the plant Aconitum napellus, conotoxins from snails, tarantula
venom toxins, saxitoxins from dinoflagellates and bacterial tetrodotoxins interfere with the function of voltage-gated ion channels, and therefore they are
strongly neurotoxic.
5 Nicotine agonizes acetylcholine at the nicotinic acetylcholine receptor (NAchR).
NAchRs are ion channels belonging to the pLIC family of pentameric ligandgated ion channels. They transmit signals from motoneurons into muscle cells at
the neuromuscular junction and between neurons in the central and peripheral
nervous system. Antagonists for these receptors include snake venoms including bungarotoxins and plant poisons such as curare and coniine. Nicotine at
doses resulting from tobacco smoking increases neurotransmitter release from
neurons in the brain, including dopaminergic neurons, explaining euphoric
and relaxing sensations due to tobacco consumption. Stimulation of adrenalin
release in the sympathetic nervous system is the cause of sympathomimetic
effects.
5 Muscimol and Thujone interact with GABA A/C -receptors. GABAergic chloride
channels are also members of the pLIC family. By gating influx of negatively
charged ions, they induce hyperpolarisation. Muscimol is produced from ibotenic acid found in poisonous fungi and acts antagonistically to GABA, inducing sedation and psychological effects. Thujone is a GABA receptor antagonist.
At high doses it induces epileptic convolutions. Synthetic drugs for GABA
receptors include barbiturates and benzodiazepines (tranquillizer).
5 Strychnine is an antagonist for glycine channels, pLICs conducting chloride
ions. Such receptors mediate feedback after muscle excitation. Strychnine thus
induces spastic muscle contractions. Tetanus toxin, by degrading SNAREs at
the same synapses, has a similar effect on muscle contraction.
5 Ketamine and PCP are synthetic drugs antagonizing glutamate receptors, more
specifically NMDA channels. They cause symptoms of schizophrenia and are hallucinogens.
5 Capsaicin and menthol interact with TRP-channels that are involved in sensing
heat and cold. . Table. 6.1 lists these ion channels, their endogenous ligands
and plant derived drugs with their mode of action on each of them.
with other temperature sensitive receptors TRPM8 is expressed in temperature sensitive
neurons, in trigeminal ganglia and dorsal root ganglia. Endogenous ligands for TRPM8
include lysophospholipids, which are products of phospholipase A-catalysed hydrolysis of
glycerophospholipids (Berridge 2012).
Interestingly, the gene encoding TRPM8 had first been isolated as a transcriptional
marker from prostate epithelial cells (Tsavaler et al. 2001). Meanwhile its expression was
also demonstrated to be up-regulated in prostate and other types of cancer (Yudin and
Rohacs 2012), but its function in cancer is not clear yet.
6.6 · TRPV and TRPM8: Heat and Cold, Capsaicin and Menthol
6
Take-Home Message
5 Aconitine from the plant Aconitum napellus, conotoxins from snails, tarantula
venom toxins, saxitoxins from dinoflagellates and bacterial tetrodotoxins interfere with the function of voltage-gated ion channels, and therefore they are
strongly neurotoxic.
5 Nicotine agonizes acetylcholine at the nicotinic acetylcholine receptor (NAchR).
NAchRs are ion channels belonging to the pLIC family of pentameric ligandgated ion channels. They transmit signals from motoneurons into muscle cells at
the neuromuscular junction and between neurons in the central and peripheral
nervous system. Antagonists for these receptors include snake venoms including bungarotoxins and plant poisons such as curare and coniine. Nicotine at
doses resulting from tobacco smoking increases neurotransmitter release from
neurons in the brain, including dopaminergic neurons, explaining euphoric
and relaxing sensations due to tobacco consumption. Stimulation of adrenalin
release in the sympathetic nervous system is the cause of sympathomimetic
effects.
5 Muscimol and Thujone interact with GABA A/C -receptors. GABAergic chloride
channels are also members of the pLIC family. By gating influx of negatively
charged ions, they induce hyperpolarisation. Muscimol is produced from ibotenic acid found in poisonous fungi and acts antagonistically to GABA, inducing sedation and psychological effects. Thujone is a GABA receptor antagonist.
At high doses it induces epileptic convolutions. Synthetic drugs for GABA
receptors include barbiturates and benzodiazepines (tranquillizer).
5 Strychnine is an antagonist for glycine channels, pLICs conducting chloride
ions. Such receptors mediate feedback after muscle excitation. Strychnine thus
induces spastic muscle contractions. Tetanus toxin, by degrading SNAREs at
the same synapses, has a similar effect on muscle contraction.
5 Ketamine and PCP are synthetic drugs antagonizing glutamate receptors, more
specifically NMDA channels. They cause symptoms of schizophrenia and are hallucinogens.
5 Capsaicin and menthol interact with TRP-channels that are involved in sensing
heat and cold. . Table. 6.1 lists these ion channels, their endogenous ligands
and plant derived drugs with their mode of action on each of them.
with other temperature sensitive receptors TRPM8 is expressed in temperature sensitive
neurons, in trigeminal ganglia and dorsal root ganglia. Endogenous ligands for TRPM8
include lysophospholipids, which are products of phospholipase A-catalysed hydrolysis of
glycerophospholipids (Berridge 2012).
Interestingly, the gene encoding TRPM8 had first been isolated as a transcriptional
marker from prostate epithelial cells (Tsavaler et al. 2001). Meanwhile its expression was
also demonstrated to be up-regulated in prostate and other types of cancer (Yudin and
Rohacs 2012), but its function in cancer is not clear yet.
6.6 · TRPV and TRPM8: Heat and Cold, Capsaicin and Menthol