Putative Peptide Neurotransmitters

The purpose of this review is to examine the present status of peptides as putative neurotransmitters. Special emphasis is placed on the evaluation of evidence for or against the transmitter role of peptides, particularly in mammalian CNS, according to the well-established criteria for transmitter identification (I, 2). The field of peptide transmitters is a new and rapidly developing one, and therefore, we can derive from the available results only tentative views as to whether or not certain peptides are likely to be transmitters. Although a number of peptides are known to influence various neural activities such as behavior and sleep (3-5), this review deals only with the peptides of known structures for which there is certain or definite neurochemical as well as electrophysiological evidence implicating their transmitter functions. The notion that certain nerve cells secrete pep tides from their axon terminals has been well known in the field of endocrinology since the early 1 950s (6). Bargmann et al (7) proposed the term peptidergic neuron for hypothalamic neurosecretory cells, and suggested that these neurons not only release peptide hormones into the blood stream but also form peptidergic synapses on endocrine epithelial cells. Re­ cent discovery of the powerful effects of physalaemin (8) and vasopressin on central neuronal activities (9) in 1971 sparked interest in the possibility that certain peptides may serve as neurotransmitters in mammalian CNS (10). This was timely because the recent progress in peptide chemistry was ready to promote the subsequent development of the field of peptide neuropharmacology. A considerable amount of data has accumulated that suggests the transmitter role of certain peptides. Particu­ larly good evidence has been obtained for two peptides, substance P and proctolin, which are described below in detail.