Effects of histrionicotoxin derivatives on ion channels and acetylcholine receptor-channel complexes in bullfrog sympathetic ganglia

Tatsuya, Ogura; Warashina, Akira

doi:10.1016/0742-8413(87)90117-4

Cited by 6 publications

(1 citation statement)

References 20 publications

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“…They have been shown to be potent non-competitive blockers of neuromuscular, 2,3 ganglionic and central neuronal nicotinic channels, 4 but as yet, the specific effect of the side chain functionalities on their activity has been the subject of only limited study. 3,5,6 Protection of Dendrobates sp. under Appendix II of CITES 7 has restricted the supply of natural material making synthetic routes greater in demand.…”

mentioning

confidence: 99%

The total synthesis of alkaloids (–)-histrionicotoxin 259A, 285C and 285EAll new compounds exhibited satisfactory spectroscopic and analytical and/or exact mass data. Electronic supplementary information (ESI) available: experimental procedures for the preparation of compounds 4, 5, 13, 16, 22 and 25. See http://www.rsc.org/suppdata/cc/b1/b111514f/

Smith

Holmes

Press³

2002

Chem. Commun.

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confidence: 99%

The total synthesis of alkaloids (–)-histrionicotoxin 259A, 285C and 285EAll new compounds exhibited satisfactory spectroscopic and analytical and/or exact mass data. Electronic supplementary information (ESI) available: experimental procedures for the preparation of compounds 4, 5, 13, 16, 22 and 25. See http://www.rsc.org/suppdata/cc/b1/b111514f/

Smith

Holmes

Press³

2002

Chem. Commun.

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Nicotinic receptor-elicited sodium flux in rat pheochromocytoma PC12 cells: Effects of agonists, antagonists, and noncompetitive blockers

et al. 1991

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Nicotinic agonists stimulate 22Na flux in rat pheochromocytoma PC12 cells. The stimulatory effect of carbamylcholine is maximal at 1 mM, while the stimulatory effect of nicotine and anatoxin maximize at the same level at 100 microM and 10 microM, respectively. The tertiary amines arecolone and isoarecolone have no effect on flux at 100 microM, while the methiodides at 100 microM stimulate flux to an extent similar to 1 mM carbamylcholine. Dihydro and alcohol analogues of isoarecolone methiodide have markedly smaller effects on flux. A preincubation for 2 to 20 min with carbamylcholine (2 mM), nicotine (300 microM), anatoxin (30 microM) or isoarecolone methiodide (100 microM) causes marked desensitization to a subsequent carbamylcholine-elicited stimulation of flux. d-Tubocurarine, mecamylamine, hexamethonium, and chlorisondamine inhibit carbamylcholine-elicited flux with IC50 values of 1.0, 0.8, 43, and 0.020 microM, respectively. Atropine has no effect at 1 microM, but reduces the response to carbamylcholine by 50% at 8.6 microM, presumably as a noncompetitive blocker. Other noncompetitive blockers of nicotinic acetylcholine-receptors, such as histrionicotoxins, gephyrotoxin, pumiliotoxin C, phencyclidine, bupivacaine and piperocaine, inhibit carbamylcholine-elicited stimulation of 22Na flux with IC50 values from 0.3 to 1.8 microM. In contrast to d-tubocurarine, which inhibits carbamylcholine-elicited desensitization, and mecamylamine, which has no apparent effect on desensitization, chlorisondamine and certain noncompetitive blockers appear to enhance desensitization. The effects of agonists, antagonists and noncompetitive blockers at the neuronal nicotinic acetylcholine receptor-channel of PC12 cells are compared to their effects on binding of [125I]alpha-bungarotoxin to agonist-recognition sites and of [3H]perhydrohistrionicotoxin to noncompetitive blocker sites of the nicotinic acetylcholine receptor-channel of electric ray (Torpedo) electroplax membranes. There are marked differences in relative potencies for the two types of nicotinic acetylcholine receptor-channel.

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Decahydroquinoline alkaloids: Noncompetitive blockers for nicotinic acetylcholine receptor-channels in pheochromocytoma cells andTorpedo electroplax

et al. 1991

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In pheochromocytoma PC12 cells, (+)-cis-decahydroquinoline 195A (5-methyl-2-propyl-cis-decahydroquinoline) and (+)-perhydro-cis-decahydroquinoline 219A (2,5-dipropyl-cis-decahydroquinoline) inhibit carbamylcholine-elicited sodium flux with IC50 values of 1.0 and 1.5 microM, respectively. Both of these decahydroquinolines appear to enhance desensitization, although apparent lack of complete removal of (+)-perhydro-cis-219A by washing complicates interpretation of the effects of that agent. A series of cis- and trans-decahydroquinolines with substituents in the 2- and 5-position also exhibit structure-dependent inhibition of carbamylcholine-elicited sodium flux in PC12 cells and all of the decahydroquinolines inhibit binding of the noncompetitive blocking agent [3H]perhydrohistrionicotoxin to muscle-type nicotinic acetylcholine receptor-channels in membranes from Torpedo electroplax. The Ki values in electroplax membranes range from 1.4 to 7.9 microM, making these alkaloids comparable in potencies to the histrionicotoxins. Potencies are increased 2- to 3-fold in the presence of an agonist, carbamylcholine. The profile of activities are similar in PC12 cells and electroplax membranes. The cis- and trans-decahydroquinolines represent another class of noncompetitive blockers for acetylcholine receptor-channels with similar activity for both muscle-type and ganglionic type nicotinic receptors.

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Effects of histrionicotoxin derivatives on ion channels and acetylcholine receptor-channel complexes in bullfrog sympathetic ganglia

Cited by 6 publications

References 20 publications

Nicotinic receptor-elicited sodium flux in rat pheochromocytoma PC12 cells: Effects of agonists, antagonists, and noncompetitive blockers

Decahydroquinoline alkaloids: Noncompetitive blockers for nicotinic acetylcholine receptor-channels in pheochromocytoma cells andTorpedo electroplax

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