Opioid peptides and pituitary function.

A number of in-vitro model systems have been introduced for the study of the action of morphine-like drugs. Their usefulness depends on their relative simplicity, compared to the brain and central nervous system, and on the good correlation observed between potencies in the models and potencies in the whole animal. For example, the contractions of the isolated guinea\x=req-\ pig ileum and mouse vas deferens to electrical stimulation at low frequencies are inhibited by opiate analgesics due to a reduced release of the motor transmitters acetylcholine (Paton, 1957) and noradrenaline (Henderson, Hughes & Kosterlitz, 1972) respectively, and the order of potencies in these smooth muscle models correlates well with the analgesic potencies of these drugs (see Kosterlitz & Waterfield, 1975). Observations with these and other model systems lead to the belief that the site of action of opiates included a specific receptor in the true, pharmacological sense; but it seemed unlikely to many workers in the field of opiate research that such apparently selective receptors should have been developed by Nature to interact with the opium alkaloids. Accordingly, the idea that the opiate receptors must be receptors for "an endogenous humoral substance" was proposed by Collier (1972). Experimental support for this hypothesis came shortly afterwards when Akil, Mayer & Liebskind (1972) reported that analgesia could be produced in rats by electrical stimulation through electrodes implanted in the periaqueductal region of the brain and that this "stimulationevoked analgesia" was reduced by administering the morphine antagonist drug naloxone. These results were taken to mean that the brain contained an endogenous substance which produced a morphine-like analgesic effect by interacting with the opiate receptor and which could be released by electrical stimulation. It was then that concerted efforts commenced in several centres to isolate the endogenous morphine-like substance.