Abstract

The regulation of prostaglandin (PG) biosynthesis by negative and positive feedback control systems is likely to prove of major importance yet surprisingly little attention has been paid to it. Little attention has also been given to selective regulation of synthesis of 1 and 2 series PGs. Such selective regulation may be important because in a number of tissues, e.g. platelets, the overall effects of 1 and 2 series products are quite different. Evidence is here presented to suggest that: a) PG12 and thromboxane (TX) A2 exert a negative feedback control over the mobilisation of arachidonic acid (AA) and its conversion to PGs. b) There are regulatory interactions between the 1 and 2 series: PGE1 inhibits AA mobilisation while TXA2 and PGE2 stimulate dihomogammalinolenic acid (DGLA) mobilisation and its conversion to PGE1. c) Contrary to what is generally believed, a surprising number of agents have actions on 1 series PG formation which are quite different from their effects on the 2 series. Inositol, angiotensin and vasopressin selectively mobilise AA. Prolactin, zinc, penicillin and levamisole selectively mobilise DGLA. Lithium selectively blocks DGLA mobilisation but at clinically relevant concentrations has little action on AA. Alcohol, vitamin C and chloroquine selectively enhance DGLA conversion to PGE1: opiates may either enhance or inhibit PGE1 formation selectively depending on receptor type. Diphenylhydantoin selectively blocks DGLA conversion to PGE1. The ways in which these selective effects may play key roles in the regulation of inflammation and immunity are discussed. In particular it is proposed that a number of inflammatory and auto-immune states arise because of a selective fall in the formation of PGE1 with a consequent rise in mobilisation of AA and the formation of 2 series PGs and leukotrienes.