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Forskolin alters acetylcholine receptor gating by a mechanism independent of adenylate cyclase activation

MM White

Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104.

The diterpene forskolin activates adenylate cyclase in a receptor- independent fashion and is commonly used to obtain a rapid elevation of intracellular cAMP levels. Application of 10-20 microM forskolin to Xenopus oocytes that express Torpedo nicotinic acetylcholine (ACh) receptors leads to an acceleration in the decay of ACh-elicited currents, which could be taken as evidence for modulation of ACh receptor gating by cAMP-dependent protein kinase. However, the effect is not mimicked by phosphodiesterase inhibitors or intracellular injection of a cAMP analog. In addition, 1,9-dideoxyforskolin, which is unable to activate adenylate cyclase, has a similar effect. Finally, the action of forskolin is rapidly reversible, with full onset and recovery occurring within the exchange time of the recording chamber. These results suggest that forskolin is a potent local anesthetic and that this property of this widely used compound must be taken into account when using it to study ion channel modulation.

Volume 34, Issue 4, pp. 427-430, 10/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics