We have used patch clamp techniques to investigate the effects of two important classes of inhibitory neuropeptides on electrical excitability of the molecular level in a tumor cell line from rat pituitary. Both classes of neuropeptides inhibit dihydropyridine-sensitive calcium channels and stimulate charybdotoxin-sensitive potassium channels by reversing the effects of cyclic AMP-dependent phosphorylation at a step distal to cyclic AMP synthesis or degradation. Experiments with phosphatase inhibitors and purified enzymes implicate the polycation-stimulated phosphoserine protein phosphatase 2A as the final common effector on both types of channel proteins. Natriuretic peptides activate phosphatase 2A through a cyclic GMP-dependent protein kinase. Many other neuropeptides, like somatostatin, that act through pertussis toxin-sensitive G-proteins, stimulate phosphatase 2A through a lipoxygenase metabolite of arachidonic acid. We are currently pursuing the generality of these novel and important inhibitory signalling pathways.
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| Storey, Nina M; Gomez-Angelats, Mireia; Bortner, Carl D et al. (2003) Stimulation of Kv1.3 potassium channels by death receptors during apoptosis in Jurkat T lymphocytes. J Biol Chem 278:33319-26 |
| Erxleben, Christian; Gomez-Alegria, Claudio; Darden, Thomas et al. (2003) Modulation of cardiac Ca(V)1.2 channels by dihydropyridine and phosphatase inhibitor requires Ser-1142 in the domain III pore loop. Proc Natl Acad Sci U S A 100:2929-34 |
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