Classical transmitters are present in all phyla that have been studied; however, our detailed understanding of the process of neurotransmission in these phyla is patchy and has centred on those neurotransmitter receptor mechanisms which are amenable to study with the tools available at the time, for example, high-affinity ligands, tissues with high density of receptor protein, suitable electrophysio-logical recording systems. Studies also clearly show that many neurones exhibit co-localization of classical transmitters and neuropeptides. However, the physiological implications of this co-localization have yet to be elucidated in the vast majority of examples.

The application of molecular biological techniques to the study of neurotransmitter receptors (to date mainly in vertebrates) is contributing to our understanding of the evolution of these proteins. Striking similarities in the structure of ligand-gated receptors have been revealed. Thus, although ligand-gated receptors differ markedly in terms of the endogenous ligands they recognize and the ion channels that they gate, the structural similarities suggest a strong evolutionary relationship. Pharmacological differences also exist between receptors that recognize the same neurotransmitter but in different phyla, and this may also be exploited to further the understanding of structure-function relationships for receptors. Thus, for instance, some invertebrate GABA receptors are similar to mammalian GABAa receptors but lack a modulatory site operated by benzodiazepines. Knowledge of the structure and subunit composition of these receptors and comparison with those that have already been elucidated for the mammalian nervous system might indicate the functional importance of certain amino acid residues or receptor subunits. These differences could also be exploited in the development of new agents to control agrochemical pests and parasites of medical importance.

The study of the pharmacology of receptor proteins for neurotransmitters in invertebrates, together with the application of biochemical and molecular biological techniques to elucidate the structure of these molecules, is now gathering momentum. For certain receptors, e.g. the nicotinic receptor, we can expect to have fundamental information on the function of this receptor at the molecular level in both invertebrates and vertebrates in the near future.

All the classical transmitter ligand molecules evolved at least 1000 million years ago. With the possible exception of the Porifera and coelenterates (Cnidaria), they occur in all the remaining phyla. All transmitters have evolved the ability to activate a range of ion channels, resulting in excitation, inhibition and biphasic or multiphasic responses. All transmitters can be synthesised in all three basic types of neurones, i.e. sensory, interneurone and motoneurone. However their relative importance as sensory, interneurone or motor transmitters varies widely between the phyla. It is likely that all neurons contain more than one type of releasable molecule, often a combination of a classical transmitter and a neuroactive peptide. Second messengers, i.e. G proteins and phospholipase C systems, appeared early in evolution and occur in all phyla that have been investigated. Although the evidence is incomplete, it is likely that all the classical transmitter receptor subtypes identified in mammals, also occur throughout the phyla. The invertebrate receptors so far cloned show some interesting homologies both between those from different invertebrate phyla and with mammalian receptors. This indicates that many of the basic receptor subtypes, including benzodiazepine subunits, evolved at an early period, probably at least 800 million years ago. Overall, the evidence stresses the similarity between the major phyla rather than their differences, supporting a common origin from primitive helminth stock.