Basic Mechanisms of Prostaglandin Action on Autonomic Neurotransmission

More than 40 years ago Euler (1) and Goldblatt (2) independently described the striking pharmacodynamic actions of human seminal plasma and extracts of sheep vesicular gland added to isolated organs or injected into the whole animal. Since the biological effects could not be accounted for by any known naturally occurring compound, the active substance(s) was named prostaglandin (3). Today prostaglan­ din (PG) is recognized, not as one, but rather a family of fatty acids of almost ubiquitous distribution in the mammalian organism. The principal biosynthetic pathways of the PGs and certain nonprostanoic compounds from their precursor, arachidonic acid, are shown in Figure 1. It should be recalled that PGs are formed from two other precursors as well, the only difference being the number of double bonds in the side chains, as indicated by the subscript numbers of the different PGs. Although the PG principle has been known for many years, it is only within the last decade that the pharmacology of the PGs has been systematically and exten­ sively investigated. These efforts, greatly aided by the availability of synthetic PGs and potent inhibitors of PG synthesis, have demonstrated that the PGs possess an impressive range of biological activities, which has given rise to many speculations concerning their physiological or pathophysiological significance. Admittedly, the PGs have distinct actions on most mammalian tissues, but few effects seem to be of the same widespread significance as those on autonomic nerves, since the auto­ nomic nervous system is such an essential regulator of the activities of a large number of organs and organ systems. There is a rapidly growing body of evidence indicating that PGs are released in the vicinity of autonomic neuroeffector junctions, both spontaneously and as a result of physical, chemical, and electrical stimuli; that PGs influence both transmitter release from nerve terminals and the response to the secreted transmitter; and that inhibitors of PG synthesis produce effects opposite to those of the POs. Taken