PEPTIDERGIC TRANSMISSION - FROM MORPHOLOGICAL CORRELATES TO FUNCTIONAL IMPLICATIONS

Like non-peptidergic transmitters, neuropeptides and their receptors d isplay a wide distribution in specific cell types of the nervous syste m. The peptides are synthesized, typically as part of a larger precurs or molecule, on the rough endoplasmic reticulum in the cell body. In t he trans-Golgi network, they are sorted to the regulated secretory pat hway, packaged into so-called large dense-core vesicles, and concentra ted. Large dense-core vesicles are preferentially located at sites dis tant from active zones of synapses. Exocytosis may occur not only at s ynaptic specializations in axonal terminals but frequently also at non synaptic release sites throughout the neuron. Large dense-core vesicle s are distinguished from small, clear synaptic vesicles, which contain 'classical' transmitters, by their morphological appearance and, part ially, their biochemical composition, the mode of stimulation required for release, the type of calcium channels involved in the exocytotic process, and the time course of recovery after stimulation. The freque ntly observed 'diffuse' release of neuropeptides and their occurrence also in areas distant to release sites is paralleled by the existence of pronounced peptide-peptide receptor mismatches found at the light m icroscopic and ultrastructural level. Coexistence of neuropeptides wit h other peptidergic and non-peptidergic substances within the same neu ron or even within the same vesicle has been established for numerous neuronal systems. In addition to exerting excitatory and inhibitory tr ansmitter-like effects and modulating the release of other neuroactive substances in the nervous system, several neuropeptides are involved in the regulation of neuronal development. Copyright (C) 1996 Elsevier Science Ltd.