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Forskolin Modulation of Desensitization at GABA(A) and Glycine Receptors Is Not Mediated by cAMP-dependent Protein Kinase in Isolated Carp Amacrine-Like Cells

Forskolin Modulation of Desensitization at GABA(A) and Glycine Receptors Is Not Mediated by cAMP-dependent Protein Kinase in Isolated Carp Amacrine-Like Cells

P Li, X L Yang

Pflugers Arch. 2001 Mar;441(6):739-45.

PMID: 11316256

Abstract:

The effects of forskolin on gamma-aminobutyric acid type-A (GABA(A)) and glycine receptors in amacrine-like cells of carp (Carassius auratus) retina were studied using patch-clamp techniques. Application of 50 microM forskolin markedly accelerated the desensitization of whole-cell responses induced by 100 microM GABA or glycine without changing the peak amplitude of the response. Both 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) and 3-isobutyl-1 -methylxanthine (IBMX) (500 microM) failed to accelerate the desensitization of these two receptors. Protein kinase A (PKA) inhibitors, N- [2-[(p-bromocinnamyl)amino]ethyl)-5-isoquinolinesulfonamide dihydrochloride (H-89) and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-8), could not block these effects of forskolin. An inactive analogue of forskolin, 1,9-dideoxyforskolin (DFSK), accelerated the desensitization effectively. These results suggest that forskolin's effects are not mediated by activation of the PKA pathway. Moreover, similar results were obtained using excised outside-out patches of these cells, suggesting that forskolin may act on an extracellular site(s). The neurosteroids 5alpha-pregnane-3alpha,21 -diol-20-one (THDOC) and 5-pregnen-31 -ol-20-one sulfate sodium (PS), structural analogues of forskolin, accelerated the desensitization of these receptors without changing the peak amplitudes, thus mimicking forskolin's effects. Furthermore, PS interacted with forskolin on these receptors so as to slow down the responses. These results raise the possibility that forskolin acts directly on an extracellular site(s) of the GABA(A) and glycine receptors, shared with neurosteroids, in carp amacrine-like cells.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP113276941-B	H-8, Dihydrochloride		113276-94-1	Price

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