The interaction of natural products with cellular signalling mechanisms

Abstract

Naturally occurring substances were of inestimable value to the founding fathers of modern pharmacology in their early studies into the nature and properties of neurotransmitter receptors. Even today, chemical substances derived from the animal and plant kingdom are of crucial importance to biochemical pharmacologists studying the mechanisms by which hormonal signals are communicated from the cell surface to the intracellular compartment. Signal transduction is a complex procedure which involves the linkage of a receptor, via a coupling protein (usually a guanine nucleotide binding protein or G-protein), to a system which produces second messengers (adenylate cyclase, phosphoinositidase C or an ion channel) or directly to an ion channel. Not only has nature provided a variety of agents that can mimic or antagonize the actions of hormones at the cell surface, but it has also provided a wealth of substances that can modify the signal transduction process at a post receptor level. In this article, we discuss the sources and the mechanisms of action of a selection of the most widely used of these latter agents and show how they have helped the modern biochemical pharmacologist to gain an insight into the fundamental mechanisms involved in signal transduction.

The source of ca2+ for the spasmolytic actions of longicaudatine, a bisindole alkaloid isolated from Strychnos trinervis (Vell.) Mart. (Loganiaceae)

“…These results suggest an important intracellular site of action for longicaudatine. Whether the alkaloid inhibits the release or promotes the sequestration and efflux of Ca2+, whether it interacts with intracellular products such as calmodulin, cyclic nucleotides (Godfraind and Miller, 1985) or with inositol tri-and tetraphosphates which are more relevant for transient contractions in smooth muscles (Rasmussen et al, 1987) are some of the questions that need to be studied. If a specific biochemical effect can be established, longicaudatine, along with other plant products such as ryanodine (Drummond and Hughes, 1987), forskolin (Seamon et al, 1981) and phorbol esters (Sasaguria and Watson, 1990), may become a useful tool to investigate signal transduction in cells.…”