Nishizawa_1990_Cell.Mol.Neurobiol_10_351

Reference

Title : Effects of forskolin and analogues on nicotinic receptor-mediated sodium flux, voltage-dependent calcium flux, and voltage-dependent rubidium efflux in pheochromocytoma PC12 cells - Nishizawa_1990_Cell.Mol.Neurobiol_10_351
Author(s) : Nishizawa Y , Seamon KB , Daly JW , Aronstam RS
Ref : Cellular Molecular Neurobiology , 10 :351 , 1990
Abstract :

1. Forskolin, a naturally occurring diterpene that activates adenylate cyclase, HL706, a water-soluble derivative of forskolin (6 beta-[(piperidino)acetoxy]-7-desacetylforskolin) that is less potent than forskolin in activating adenylate cyclase, and 1,9-dideoxyforskolin, an analogue that does not activate adenylate cyclase, were examined for effects on the nicotinic receptor-mediated 22Na+ flux, a high potassium-induced 45Ca2+ flux through L-type calcium channels, and a high potassium-induced 86Rb+ efflux through a calcium-dependent potassium channels in PC12 cells. 2. Forskolin and analogues at 30 microM completely blocked carbamylcholine-elicited flux of 22Na+ through the nicotinic receptor-gated channel. 1,9-Dideoxyforskolin had an IC50 value of 1.6 microM with forskolin and HL706 being two- to three fold less potent. 3. Forskolin and its analogues appear to be noncompetitive blockers of the neuronal nicotinic receptor-channel complex in PC12 cells, but unlike many noncompetitive blockers, did not markedly enhance desensitization. Instead, forskolin, but not HL706 or 1,9-dideoxyforskolin, slightly antagonized the desensitization evoked by high concentrations of carbamylcholine. N-Ethylcarboxamidoadenosine, an adenosine analogue that elevates cyclic AMP and 8-bromo-cyclic AMP had no effect on desensitization. 4. Forskolin, HL706, and 1,9-dideoxyforskolin in the presence of carbamylcholine inhibited the binding of a noncompetitive blocker, [3H]perhydrohistrionicotoxin, to the muscle-type nicotinic receptor-channel complex in Torpedo electroplax membranes with IC50 values of 20 microM. Forskolin had no effect on [3H]perhydrohistrionicotoxin binding in the absence of carbamylcholine, while HL706 and 1,9-dideoxyforskolin still inhibited binding in the absence of carbamylcholine. 5. Forskolin, but not HL706 or 1,9-dideoxyforskolin had a slight inhibitory effect on the binding of [125I]alpha-bungarotoxin to acetylcholine recognition sites in Torpedo membranes. 1,9-Dideoxyforskolin at 30 microM, but not forskolin or HL706, markedly inhibited depolarization-evoked 45Ca+ flux and 86Rb+ efflux in PC12 cells, suggesting that 1,9-dideoxyforskolin has nonspecific inhibitory effects on a variety of ion channels.

PubMedSearch : Nishizawa_1990_Cell.Mol.Neurobiol_10_351
PubMedID: 1701359

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Citations formats

Nishizawa Y, Seamon KB, Daly JW, Aronstam RS (1990)
Effects of forskolin and analogues on nicotinic receptor-mediated sodium flux, voltage-dependent calcium flux, and voltage-dependent rubidium efflux in pheochromocytoma PC12 cells
Cellular Molecular Neurobiology 10 :351

Nishizawa Y, Seamon KB, Daly JW, Aronstam RS (1990)
Cellular Molecular Neurobiology 10 :351