AIMS OF THE STUDY

As outlined in the previous section, cotinine pharmacologically acts on neural systems, but its effects remain obscure. Since cotinine is structurally related to nicotine, its probable targets include nicotinic receptors, through which it can modify nicotinic responses. PLD, in turn, is a good candidate for catalysing the nicotine-evoked prolonged diglyceride production and sustaining the increased PKC activity. The finding - presented in a single report at the time this work was planned - that PLD is lacking from bovine chromaffin cells does not concur with this hypothesis. If PLD activity exists in chromaffin cells, it may well have a role in nicotinic signalling.

The aim of the present study was to clarify whether:

1. receptor-linked PLD activity exists in bovine adrenal chromaffin cells;
2. PLD participates in nicotine signalling, especially in sustained kinase activation;
3. cotinine modulates the effects of nicotine on intracellular (PKC activity, [Ca⁺⁺]_i) and intercellular (noradrenaline release) chromaffin cell signalling;
4. cotinine itself evokes chromaffin cell responses; and
5. cotinine effects are mediated by nicotinic acetylcholine receptors.