Peptides as putative excitatory neurotransmitters: carnosine, enkephalin, substance P and TRH

A number of in vitro preparations of the central nervous system have been used to characterize with intracellular recording the cellular actions of four neuropeptides. Carnosine, the putative excitatory neurotransmitter of olfactory nerves, was found to exert little or no effect in the turtle or the frog olfactory bulb, suggesting that this peptide may have other roles, e.g. neurotropic, in this system. Substance P and TRH were found to have some characteristics of a classical excitatory transmitter since they increase membrane conductance and depolarize frog motoneurons by a direct action. However, the slow time course and subthreshold nature of the depolarization may imply that these peptides function in a background manner to set the level of excitability of motoneurons. Finally, the effects of enkephalin on a variety of inhibitory systems have been examined. Enkephalin excites hippocampal pyramidal cells indirectly by blocking both spontaneous and evoked inhibitory potentials. In addition, both feedforward and feedback inhibitory pathways are depressed by enkephalin. All these effects are blocked by naloxone. Blockade of inhibitory pathways by enkephalin appears to be a general phenomenon, since similar depressant effects were seen for dendrodendritic inhibition in olfactory bulb mitral cells as well as for presynaptic inhibition of spinal primary afferents. These results indicate that neuroactive peptides can affect principal neurons by increasing their excitability via either subthreshold excitation or disinhibition.