ISSN:
1573-6830
Schlagwort(e):
forskolin
;
carbamylcholine
;
nicotinic receptor-channels
;
voltage-dependent channels
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Biologie
Notizen:
Summary 1. Forskolin, a naturally occurring diterpene that activates adenylate cyclase, HL706, a water-soluble derivative of forskolin (6β-[(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-mediated22Na+ flux, a high potassium-induced45Ca2+ flux throughL-type calcium channels, and a high potassium-induced86Rb+ efflux through a calcium-dependent potassium channels in PC12 cells. 2. Forskolin and analogues at 30µM completely blocked carbamylcholine-elicited flux of22Na+ through the nicotinic receptor-gated channel. 1,9-Dideoxyforskolin had an IC50 value of 1.6µM 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 inTorpedo electroplax membranes with IC50 values of 20µM. 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]α-bungarotoxin to acetylcholine recognition sites inTorpedo membranes. 1,9-Dideoxyforskolin at 30µM, but not forskolin or HL706, markedly inhibited depolarization-evoked45Ca+ flux and86Rb+ efflux in PC12 cells, suggesting that 1,9-dideoxyforskolin has nonspecific inhibitory effects on a variety of ion channels.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00711180
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