Functionally opposite receptors on neurones.

According to the second general principle of chemical neurotransmission, formulated by Eccles, a neurotransmitter released from the axonal terminals of a neurone has only one and the same effect on all the follower cells: all the follower cells are either excited or inhibited by it. The evidence reviewed in this paper suggests that there may be some exceptions to this general pattern of synaptic organisation. The co-existence of both excitatory and inhibitory receptors for the same transmitter substance on the same neuronal membrane has been described in invertebrates: ‘opposite receptors’ can occur for acetylcholine, dopamine and glutamate. There is also evidence suggesting the existence of opposite receptors for acetylcholine and nonadrenaline on neurones in the mammalian brain. The activation of functionally opposite receptors results in ‘antagonistic agonism’: the net pharmacological effect is obtained by the algebraic summation of the two opposing component effects. Both the time-course and the polarity of neuronal responses to a given neurotransmitter is influenced by the relationship between the two kinds of receptor. It is suggested that both pre-synaptic and post-synaptic factors may modify this relationship.