Cholinergic phosphatidylinositol modulation of inhibitory, G protein-linked neurotransmitter actions:...

In electrophysiological studies using the rat hippocampal slice preparation, cholinergic agonists and phorbol 12,13-diacetate, a stimulator of protein kinase C, block the inhibitory actions of baclofen, a gamma-aminobutyric acid B receptor agonist, and adenosine. Relative potencies of cholinergic agonists in stimulating the phosphatidylinositol system, as measured biochemically, parallel their activity in blocking adenosine assessed electrophysiologically. Electrical stimulation of cholinergic afferents also reverses adenosine's inhibitory action. These findings indicate that stimulation of protein kinase C by the phosphatidylinositol system mediates cholinergic blockade of adenosine and baclofen. As these inhibitory agonists act by way of receptors linked to GTP-binding proteins, protein kinase C's inactivation of the GTP-binding protein involved may account for this cholinergic action.